chapter 4 abstract cancer associated dyslipidemia€¦ · advances in dyslipidemia advances in...

2 3www.avidscience.com

Advances in Dyslipidemia Advances in Dyslipidemia

www.avidscience.com

AbstractDyslipidemia in cancer patients is reported to be

linked with cancer risk and progression of the disease. Previous research findings showed that low levels of se-rum cholesterol and elevated levels of serum triglycerides are associated with risk of overall cancers. However, there are several inconsistencies in the reports regarding the as-sociation of dyslipidemia with cancers. In this book chap-ter we will emphasize on dyslipidemia in relationship to the cancer risk, diagnosis, prognosis and mortality inci-dents.

KeywordsSerum lipids; Plasma lipids; Cancer; Dyslipidemia;

Lipoproteins; Cholesterol; TG; LDL; HDL; VLDL

AbbreviationsTC-Total Cholesterol; TGs-Triglycerides; TG-Triglyc-

eride; HDL-High Density Lipoprotein; VLDL-Very Low Density Lipoprotein; LDL-Low Density Lipoprotein

IntroductionResearch on the biochemistry and molecular biol-

ogy of lipids and lipoproteins has experienced remarkable growth in the past years, particularly with the realization that different classes of lipoproteins play fundamental roles in diseases such as cardiovascular diseases, obesity, diabetes, cancer and several neurodegenerative disorders.

Chapter 4

Cancer Associated Dyslipidemia

Hina Usman1*, Rimsha Munir1, Fatima Ameer1 and Shahida Hasnain1

1 Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan

*Corresponding Author: Hina Usman, Microbiology and Molecular Genetics, University of the Punjab, La-hore-54590, Pakistan, Tel: 0092-334-9862501 ; Fax: 35952855; Email: [email protected]

First Published April 02, 2016

Copyright: © 2016 Hina Usman et al.

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source.



www.avidscience.com

Aberrant blood lipid profiles/dyslipidemia has long been considered as the risk factor of cardiovascular dis-eases. More recently, various research findings revealed that dyslipidemia is also associated with cancer [1-5]. It has also been known that lipids play crucial role in tumor development and progression [4,6]. The malignant cells manipulate and up-regulate their lipogenic and lipolytic pathways for acquisition of lipids [7,8]. As lipoproteins are the distributors of both endogenous as well as exogenous lipids across the tissues therefore it is suggested that dereg-ulation of lipid metabolic pathways may also affect plasma levels of lipoproteins. Previous studies have demonstrated that almost all cancers are affected with aberrant serum/plasma lipid levels. Serum/plasma lipids-total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL) and triglycerides (TGs) are suggested to be associated with cancer development and progression [1-3]. However, there are several discrep-ancies in the reports regarding the association of dyslipi-demia with cancers. The reasons for these inconsistencies in previous research reports might be observed due to the types of cancer or due to related confounding factors in-cluding, lifestyle, obesity [5] and effect of antineoplastic therapies [9]. One of the reasons for these contradictory reports could be the fact that various types of cancers ex-ploit different modes for the acquisition of lipids that in turn affect the serum/plasma lipid profiles.

In this chapter we will review the association between dyslipidemia and risk of developing various types of can-cers including both hematopoietic malignancies and solid tumors. In order to gain more insight into this complex in-terplay, some prospective underlying mechanisms will be addressed. Moreover, the potential roles of serum/plasma lipids in promoting carcinogenesis will also be conferred.

Solid TumorsPrevious works have demonstrated that cancer pa-

tients often display aberrant blood lipid profiles (Table 1). Researchers have also reported association of plasma/se-rum lipids and lipoproteins with different types of cancers (Table 1). In the subsequent sections we will discuss this association between plasma lipid levels and solids cancers in detail.

Breast CancerBreast cancer is a heterogeneous disease which is fur-

ther subdivided into different tumor types on the basis of molecular profile of tumors, patient prognosis and treat-ment options. Breast cancer is also associated with differ-ent cofactors which add up the disease burden such as age, menopausal status, blood lipid profiles and obesity [10]. Abnormal lipid profiles or dyslipidemia are considered as one of the major risk factor of breast cancer.



www.avidscience.com

Many epidemiological studies revealed that breast cancer patients display significantly elevated levels of serum cholesterol [11]. But these observations are not consistent, for example, few longitudinal studies showed that high serum cholesterol levels were associated with in-creased risk of breast cancer [11]. While some breast can-cer related studies showed no association between breast cancer risk and cholesterol [11].

The most striking and frequent of these observations is that; low levels of serum HDL are associated with in-creased risk of all cancers [11]. There are very few contra-dictory studies that showed that increased risk of cancer is associated with high levels of serum HDL. For instance it has been reported that women with breast cancer display high levels of HDL in comparison to the healthy women [11]. Although breast cancer patients display reverse re-lationship; here increased LDL levels are associated with increased breast cancer risk [11].

Moreover, it has been reported that serum lipid pro-files of the breast cancer patients with metabolic syndrome are different from those without metabolic syndrome [11]. It has been shown that total cholesterol and triglyceride content in breast cancer patients without metabolic syn-drome lies within the normal range [11]. Besides higher levels of serum HDL are shown to be inversely associated with the risk of breast cancer in premenopausal women [11]. Some of the previous works have also studied the possible association of tumor stage or grade with serum

lipid profile. It has been shown that breast cancer patients with advanced disease in comparison to the patients with less advanced disease and controls display significantly higher serum TGs and significantly lower serum choles-terol and HDL levels. Moreover, lower serum LDL levels were observed in breast cancer patients with bony metas-tasis as compared to the patients with liver or liver bony metastasis [11].

Now question arises, how dyslipidemia is associated with the risk of breast cancer? It has been well studied that breast cancer cells have lipogenic phenotype (use de novo fatty acid synthesis pathway). Also, it has been reported that risk of breast cancer is 5 times higher in women of western countries as compared to the Asian women [12]. Moreover, relocation and migrational studies have dem-onstrated that migration from a region with low incidence to a region with high incidence increases breast cancer incidence in the immigrant population [13]. These epi-demiological studies strongly indicated that risk of breast cancer is associated with the diet pattern of women. So, it is hypothesized that dietary lipids might favor the oc-currence and progression of breast cancer. Plasma lipo-proteins are the major distributor of dietary lipids there-fore; blood lipid profiles could be utilized for accessing the early diagnosis and future outcome (prognosis) of disease.



www.avidscience.com

Prostate CancerSeveral epidemiological studies have demonstrated

that risk of developing prostate cancer is closely associated with dietary fat consumption [14,15]. In addition to this fat intake also supports the progression of prostate cancer [15]. Fat consumption directly affects the blood lipid pro-file of an individual therefore; it is suggest that blood lipid profiles might be helpful in early diagnosis of malignant disease.

Several recent research works support inverse asso-ciation between the intake of statins and advanced stage prostate cancer [11], whereas some reports negate these findings. It has been proposed that the prostate cancer cells exhibit cholesterol feedback dysregulation, hence they might display increased sensitivity to statins [11].

To study the possible and direct role of cholesterol in this observed inverse association between statin intake and advanced stage prostate cancer, a nested case control study was carried out. It was reported that men with low plasma cholesterol had a lower-risk of high-grade pros-tate cancer and possibly advanced stage disease, but not organ-confined or low-grade disease [11]. Exclusion of the statin-users did not alter these results indicating a direct role of cholesterol in mediating this inverse asso-ciation between statin intake and advanced stage prostate cancer. Another recent work where statin users were ex-cluded from the study population suggests that men with

low cholesterol have a reduced risk of high-grade prostate cancer [11].

Gastrointestinal CancersAs dyslipidemia is an established risk factor for the

other cancers, its role in gastrointestinal malignancies is also well studied. The increasing prevalence of oesopha-geal, stomach, colon, and rectal cancers may be attributed by plasma/serum lipids. The fat-rich diets, at quantities of 40 to 45% of the total calories ingested by the population, have a close relationship with colorectal cancer incidence [16]. There are several prospective and cohort studies that show conflicting results about colorectal cancers. Here, we present a review of most discrepant findings and their possible explanations.

The main findings of a recent case–cohort study nest-ed in an Italian multicentre cohort suggested that high lev-els of plasma total and LDL cholesterol increase colorec-tal cancer risk, particularly in men and postmenopausal women [17]. Another Swedish Apolipoprotein Mortality Risk (AMORIS) cohort study also showed parallel results of total cholesterol (TC) with Italian multicentre cohort study. According to this study, high TC levels were asso-ciated with an increased rectal cancer risk whereas high glucose and TG levels were associated with an increased colon cancer risk. An increased risk of oesophageal can-cer was also observed in persons with high TG and low LDL, LDL/HDL ratio, TC/HDL ratio, log (TG/HDL),



www.avidscience.com

and apoB/apoAI ratio [18]. According to Wulaningsihet al., 2012, the persistent link between TC and rectal can-cer risk as well as between TG and colon and oesophageal cancer risk in normoglycaemic individuals may imply their substantiality in gastrointestinal carcinogenesis [18]. A large prospective study in Korea 2011- restricted to men only-[19] and a study in Sweden 2009 [20] found mod-est positive association of serum TC with colon cancer. Another study showed positive correlation of serum levels of TC and LDL fraction with the appearance of colorectal cancer [20]. Although the exact mechanisms that how the high total cholesterol levels could lead to an increased risk of colorectal cancers are unclear. McKeown-Eyssen (1994) has also reported an association between high serum tri-glyceride and colon cancer [21].

In contrast, there are some reports that depict inverse association between blood lipids and colorectal cancers. For example, a study in 1974 [22] which pooled cohort cases from six prospective cardiovascular studies on men, found that the 90 colon cancer cases had lower mean se-rum cholesterol level than the overall cohort mean. A 1983 review also found an inverse relationship between blood cholesterol and colon cancer [23] as did the Framingham [24] and Honolulu Heart [25] studies. In a cross sectional study, lowest serum TG levels were revealed in colorectal cancers [26]. A large number of prospective studies gen-erally do not support an association between cholesterol and risk of colorectal cancer [19,20,27-31]. The1991 re-view of prospective studies found no long-term associa-

tion of colorectal cancer with low cholesterol [32].

One of the major causes for these aberrant lipid pat-terns could be the metabolic syndrome; characterized by three or more components among abdominal obesity, high blood pressure, hyperglycemia, hypertriglyceridemia, and low HDL cholesterol [17]. Some recent prospective stud-ies have found that people with metabolic syndrome are at an increased risk of developing colorectal cancer [15,16]. There are several possible mechanisms; mainly involving abdominal obesity and insulin resistance that have been proposed to link the syndrome with colorectal cancer [18]. In particular, the dyslipidemia component of meta-bolic syndrome is linked to chronic low grade inflamma-tion [19], oxidative stress [20] and insulin resistance [21]–all of which may enhance carcinogenesis. However, some prospective studies exploring the relation of alterations in individual components of blood lipids with colorec-tal cancer have yielded conflicting results [17,31,33-39]. It is also possible that some genetic factors that affect the metabolism of cholesterol also influence susceptibility to cancer [40]. Hence, apolipoprotein E (apo E) - a multi-functional protein with a role in the transport and me-tabolism of lipids [40] - has also been considered in the etiology of colorectal cancer [41-43]. In a Brazilian study, the patients had statistically non-significant reduced lev-els (mean ± SD) of TC and LDL (180.4 ± 49.5 and 116.1 ± 43.1 mg/dL, respectively) compared to controls (204.2 ± 55.6, P = 0.135 and 134.7 ± 50.8 mg/dL; P = 0.330, respec-tively). The study concluded that presence of the ε4/ε4



www.avidscience.com

genotype only in controls may serve as a protective against colorectal cancers. Lower lipid profile values among pa-tients, even those on lipid-rich diets associated with the APOE*4 allele, suggest alterations in the lipid synthesis and metabolism pathways in colorectal cancers [40].

Hence, on the basis of these studies no clear-cut asso-ciation between colorectal cancer progression and chang-es in blood levels of lipids can be decisively stated. For instance, some studies showed a decrease in plasma lipid levels in patients with colorectal cancers, when compared to controls. On the other hand, we have quite a number of reports supporting the opposite association. This may be a consequent upon an increased utilization of blood lipids by malignant cells as a competing factor [44] or some oth-er possible metabolic variability. To understand the role of dyslipidemia in gastrointestinal malignancies, we need to monitor several confounding factors such as classification of cancers, gender, age and body mass index etc.

Liver cancersLiver cancer is a major public health concern and was

considered as fifth common malignant tumor worldwide [45]. It is well known for its poor prognosis. Many pre-vious studies indicate that lower cholesterol levels might increase the risk of cancers. However, this pattern is only consistent in case of preclinical cancers not in all cancers [46,47]. Following this pattern, the patients with severe hepatitis or hepatic failure or chronic liver disease also manifest decline in serum/plasma total cholesterol, TG,

HDL, LDL and VLDL cholesterol levels in comparison to the controls [48-61]. This phenomenon could be attrib-uted to the decreased lipoprotein biosynthesis [62]. The negative association between LDL and liver cancer mor-tality has also been observed in a previous report; show-ing that low LDL cholesterol may be a predictive marker for death due to liver cancer [50]. Jiang et al., 2008 also reported significantly decreased serum TG, apoAI, HDL and Lp(a) in hepatocellular carcinoma (HCC) patients than in controls, whereas plasma apoM levels were sig-nificantly increased in the HCC patients [63]. Moreover, these above mentioned studies were done on a large group of participants and were not gender restricted [46,50]. Though, this would be of prodigious significance to asso-ciate dyslipidemia in liver cancer patients with the severity of the disease.

Liver is the main organ that is involved in lipid me-tabolism. Lipid accumulation in the liver is known as one of the factors for HCC. Liver cancer is followed by liver cirrhosis or chronic hepatitis that may significantly influ-ence lipid and lipoprotein metabolism in vivo [64] and so lowers serum cholesterol [28]. Serum/plasma lipid or li-poprotein levels in liver could be disordered due to cancer, cirrhosis, blocked esterification and evacuation of choles-terol in liver [65-71].



www.avidscience.com

The reduction of TG levels in liver cancers observed by Motta et al. (2001), may be explained on the basis of the relationship between cytokines and lipids [72]. Tumor cells produce such as Tnf-α, IL-1, IL-6, and IFN-α [73,74] that inhibit lipolysis [75]. Hepatic TG lipase activity was also found significantly decreased in hepatocarcinogen-esis [76].

Serum Lp(a) level in liver cancer patients decreased strikingly as compared with that of the normal. Lp(a); produced by the liver its malfunction in liver cells may de-crease its levels in patients with chronic liver disease [77]. The cause may be involvement of hormones, cytokines, genetics and nutrition in different ways because these in-fluence serum Lp(a) levels in tumors by inducing cachexia that may disorder lipid metabolism [73,78]. Nevertheless, Lp(a) is synthesized and metabolized independently of other plasma lipoproteins so it is not influenced by various dietary manipulations [79]. Lp(a) is a substance involved in both lipid and proteic metabolism, and can be a sensi-tive and early marker of liver malfunction. It is concluded that Lp(a) might be useful in the follow-up of liver cancer patients and can be used for evaluation of the liver func-tion [66], but in another study the increased Lp(a) serum level was found in hepatoma patients [80].

The quantitative and qualitative difference of lipids, apolipoproteins, enzymes, and lipid transfer proteins results due to various HDL subclasses, which are char-acterized by differences in shape, density, size, charge

and antigenicity [81]. Cholesterol ester transfer protein (CETP) - an important determinant of lipoprotein func-tion especially HDL metabolism–regulates plasma HDL levels [82]. Therefore, HDL plays a key role in the reverse cholesterol transport pathway in liver [83,84]. The pri-mary site of human HDL synthesis is believed to be in the liver [85,86]. Ooiet al. (2005) analyzed lipids in liver dis-eases such as lower HDL-fraction and higher levels of all other parameters in case of metastatic liver as compared to HCC [67]. Slow α-HDL, abnormal LDL, Lp-X (lipo-protein X) and Lp-Y (lipoprotein Y) were found associ-ated with liver diseases. Slow alpha HDL appeared during slight bile stagnation and was accompanied by increase in the apoE level and the HDL particle size [67]. Hepatic lipase (HL) can adversely affect the HDL2 selectively; hy-drolyze the TG and lipoprotein in it [87]. The transgenic over expression of HL in either mice or rabbits decreased HDL levels [88,89]. HL activity is suppressed by estradiol and increased by testosterone [90,91], and when patients’ estradiol level with HCC was high, the secreting ability of testosterone will be cut down, which decreases HDL level too.

Moreover some findings showed virus induced he-patic carcinomas with lower serum cholesterol, TG, HDL and LDL levels [54,92-94]. The possible mechanism be-hind significantly lower serum cholesterol levels in pa-tients with liver cancer has been clearly explained by Jiang et al., (2007). As liver cancer progresses, tumor cells intake



www.avidscience.com

much exogenous cholesterol that affects endogenous cho-lesterol to its pathogenic extent [95], and then using this for cytomembrane synthesis [96], duplication of DNA and regulation of oncogene protein [97]. With the reduced synthesis of hydroxy-methylglutarylcoenzyme A (HMG-CoA) reductase, cholesterol synthesis in liver is also re-duced and serum cholesterol content gradually depressed, especially in liver cancer [65,67]. Additionally, HDL caus-es serum cholesterol level to significantly decrease in liver cancer [66]. Moreover, the X protein of hepatitis B virus (HBx)–over expressed in HCC-was shown to down-reg-ulate the transcriptional level of microsomal triglyceride transfer protein, which regulates the assembly and secre-tion of apoB. Apolipoprotein B (apoB) in the liver is an important glycoprotein for transport of VLDL and LDL. In liver cells hyper-express of HBx, but serum TG level in liver cancer did not obviously decrease compared with Lp(a), total cholesterol and HDL [67].

In most of these above findings, significant negative association of liver cancer incidence and mortality with lower levels of serum/plasma total cholesterol, HDL and LDL was shown but not with TG levels [32,54,98]. Lower HDL levels in Child-Pugh C than Child-Pugh B and in Child-Pugh B than Child-Pugh A and apo-A levels were also found to be the most affected factors in those with liver damage [55].

The study of the argument that there is an association between dyslipidemia and liver cancer showed that condi-tion of liver lipid and lipoprotein metabolism and hepatic cell impairment are related, and will aid in determination of pathogenetic condition, therapeutic effect and progno-sis in liver cancer.

Hematopoietic MalignanciesNumerous studies have reported alterations in the

plasma lipid profiles in patients with hematopoietic ma-lignancies. However, there are several inconsistencies in these reports [99-104]. The underlying mechanisms for these irregularities have not been clearly elucidated. In general, lipids are known to play a crucial role in tumor development and progression [6]. Lipoproteins are the distributors of both endogenous as well as exogenous li-pids across the tissues. Therefore, it is plausible that lipo-proteins play a fundamental role in cancer progression via supplying lipids to malignant cells and tumors. These speculations are even more intriguing for the leukemic cells that are in circulation and could attain more direct benefit from the plasma lipoproteins.

LeukemiaSeveral prospective-cohort studies have previously

reported that lower levels of serum cholesterol are asso-ciated with high-risk of developing leukemia as well as overall hematopoietic cancers [27,29,105-107] (Table 1).



www.avidscience.com

Moreover, low plasma cholesterol levels were found to be associated with increased risk of mortality in hematopoi-etic cancer patients [108]. On the contrary, there are few studies that report no association between total serum cholesterol levels and the risk of leukemia [28,109].

The exact cause of the abnormal lipid profiles in leu-kemia patients is not yet clearly elucidated. The possible role of plasma lipids and lipoproteins in carcinogenesis is also not very well-defined. However, researchers working in this area have made number of suggestions to explain the aberrant plasma lipid profile in leukemia patients [11]. The increased uptake and degradation of LDL cholestero-lis widely reported in acute myeloid leukemia (AML) cells [110,111]. Thus, it can be speculated that increased uptake of LDL by cancer cells may affect its clearance from cir-culation and results in decreased serum LDL levels in the cancer patients. Leukemia cells were also shown to display higher uptake of HDL-cholesteryl esters [112]. It has also been reported that the conversion of cholesterol to bile acids is suppressed in the AML patients, a phenomenon that may also result in a decreased intestinal absorption of cholesterol and subsequent hypocholesterolemia [113].

The fatty acid analysis of the triglyceride esters in se-rum of leukemia patients revealed a high proportion of stearic-acid (18:0) [114], which is associated with a slower in vitro degradation of VLDL by (LPL). Hence, the ab-normal composition of triglycerides renders VLDL a poor substrate for lipoprotein lipase (LPL) that may also cause

increased serum TG and VLDL levels in leukemia pa-tients.

All of the above mentioned works indicate that the aberrant lipid profiles in leukemia patients are possibly a consequence of cancer. However, several studies have clearly associated the risk of developing leukemia with atypical serum lipoprotein levels (Table 2). Hence, a caus-ative role of aberrant lipoprotein levels is also suggested by previous reports, at least for the malignancies of non-hematopoietic origins. Some researchers have suggested that peroxidation of plasma lipoproteins may also play a key role in cancer development [115]. Lipoproteins are susceptible to peroxidation triggered by reactive oxygen species and reactive nitrogen species. It has been pro-posed that lipid peroxidation product malondialdehyde, that form adducts with adenosine and cytosine, may con-tribute to mutagenicity and carcinogenicity in mamma-lian cells [116]. On the other hand, HDL that-due to its lipid and apoprotein content - is less susceptible to per-oxidation in comparison to LDL, counters the oxidative damage caused by oxidized LDL [117]. Thereby, HDL pre-vents the generation of reactive oxygen species and acts as an anti-carcinogen. These speculations provide a possible explanation for the involvement of plasma lipoproteins in carcinogenesis however; further studies are required for the better understanding of this phenomenon.



www.avidscience.com

Multiple MyelomaMyeloma is the cancer of the plasma cells-white blood

cells that produce antibodies. Myeloma cells are produced in the bone marrow. Myeloma cells prevent the normal production of antibodies that makes the immune system weak. Hence the patient is susceptible to infections. The multiplication of myeloma cells also hinders the normal production and function of normal blood cells. In most cases of myeloma there is an excessive production of M-proteins or paraproteins–abnormal antibodies that can cause kidney damage. Additionally, the myeloma cells normally produce substances that may cause bone de-struction, leading to bone pain and/or fractures.

Like several solid tumors, hypocholestrolemia is also observed in some types of hematological malignancies, e.g. multiple myeloma (MM). As compared to healthy individuals serum total cholesterol, HDL and LDL levels were found to be significantly lowered in MM patients (p<0.001). Whereas, no difference was observed when TG and VLDL levels were compared between the both groups [118]. Serum lipid levels are also shown to be affected by the type and stage of multiple myeloma [118,119]. One of the plausible reason for hypocholestrolemia in MM pa-tients, could be the increased clearance of LDL and utili-zation of cholesterol by the myeloma cells [118].

LymphomaLymphoma is a form of hematopoietic cancer of lym-

phoid origin. It involves lymph nodes and immune cells-lymphocytes. The two major types are Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL). Like several other types of blood cancers, lymphoma patients often exhibit aberrant lipid metabolism. Previously Lim et al. reported that decreased circulation of HDL particles may take place during lymphomagenesis. However, no correla-tion for total and non-HDL cholesterol was observed in NHL patients. The inverse association observed between HDL and NHL changed during the follow-up period. It wasn’t confounded by factors like obesity (a putative risk factor for NHL) and physical activity but the gender of the patient affected this association [120]. Further investiga-tions should be conducted to evaluate the etiological role of serum lipids in lymphomagenesis.

ConclusionDyslipidemia in cancer patients is reported to be as-

sociated with cancer risk, pathogenesis and progression [121,122]. However, there are several discrepancies in the previous reports. Hence the clinical usefulness of plasma/serum lipid levels in risk stratification of a variety of can-cers remains elusive. There are several environmental and genetic factors that are known to influence human plasma lipid profile [123]. It is quite possible that the divergent



www.avidscience.com

findings from the previous studies - regarding association between plasma lipid levels and cancers - are due to the fact that these confounding factors were overlooked dur-ing analyses. Moreover, these findings may help in out-lining the prevalence and types of dyslipidemia in cancer patients that may emerge as diagnostic/prognostic factors for the management of cancer. This knowledge will lead us to the new therapeutic strategies for treatment of cancer. Further investigations are required to clarify this associa-tion.

AcknowledgementsThis work from the author’s laboratory was support-

ed/funded by Higher Education Commission, Pakistan. (H Usman). We gratefully acknowledge Rida Rashid for review of this chapter.

Table 1: Overview of the previous studies aimed to evalu-ate the association between plasma/serum of various lipid

fractions and cancer.Cancer

Type Studied

Reference Lipid Fraction Studied Cancer Subtype Sample Size Results/Comments

Ove

rall/

Seve

ral C

ance

rs

[124] Chl - N = 577,330 Lower serum Chl levels were associated with high-risk of all cancers in females. This association is also observed in males for several types of cancers.

[125] Chl and LDL - n = 100

c = 103

Significantly lower levels of total serum Chl, esteri-fied-Chl and LDL were observed in patients in com-parison to the control population.

[126] Chl - n = 61

c = 610

Lower levels of serum Chl were observed in patients in comparison to the control population.

[127] Chl - c(Stomach cancer) = 557

c(Colorectal cancer) = 506

c(Lung cancer) = 320

c(Breast cancer) = 178

c(Prostate cancer) = 164

c(Liver cancer) =125

c(Cervical cancer) =55

c(Leukemia) =50

Lower levels of serum Chl were associated with high-risk of all cancers analyzed, particularly, sto-mach and liver.

[128] Chl - c (Non-Survivors) = 290

c (Survivors)= 2,173

There was no significant difference between plasma Chl levels of the survivors and non-survivors. No-netheless, increased mortality was associated with low plasma Chl levels in lung cancer patients but not in stomach, prostate or colon cancer patients.

[129] Chl and TGs - n = 131

c = 131

In comparison to the control population male cancer patients displayed lower whereas, female cancer patients displayed higher plasma Chllevels. TG levels were not significantly different between cancer pa-tients and controls.

[130] LDL - N = 6,107 In type 2 diabetes patients the association between LDL and cancer was V-shaped, whereby both low and high levels of LDL were associated with elevated risk of cancer.

[131] Chl - N = 172,210 High serum Chl levels were associated with lower cancer risk.

[132] Chl, LDL and TGs - c(Lymphomas) = 18

c(Breast carcinomas) = 18

c(Small-cell lung carcinomas) = 14

c(Urothelial-cell carcinoma)= 7

In this study various cancer patients undergoing chemotherapy were included. Patients that res-ponded positively to chemotherapy demonstrated a significant increase in serum Chl, TG and LDL levels. While breast cancer patients responding po-sitively to chemotherapy displayed a non- significant decrease in Chl and LDL.

[133] Chl, HDL, LDL, TGs, α-lipoproteins, Phospholipids and Total lipids

- n = 60

c = 115

Serum Chl, HDL, LDL, total lipids, phospholipids and α-lipoproteins levels were significantly lower in pa-tients as compared to the control group, whereas TG levels were found to be significantly elevated.

[134] Chl - c = 160,135 There was no strong or consistent association between low serum Chl level and overall cancer incidence. Lower serum Chl levels were only as-sociated with elevated risks of cervical cancer and lymphoma in males.

[135] Chl, LDL and VLDL - c = 4,224 Significantly lower plasma Chl values were obser-ved in colorectal and gastric carcinoma patients as compared to the controls. While for other cancers no significant difference in plasma lipid fractions was observed.

[136] Chl, HDL, TGs and LDL - n = 415

c(Hematological malignancies) = 97 c(Lung cancer) = 92

c(Cancer of upper digestive system) = 108

c(Colon cancer) = 103

c(Breast cancer) = 32

c( Cancer of the genitourinary system) = 32

Significantly lower serum Chl, LDL and HDL levels were observed in all cancer patients in comparison to the controls. The lowest values of Chl, LDL and HDL were recorded in patients with hematological malignancies. Multiple regression analysis showed that cancer is also associated with high values of serum TG levels.



www.avidscience.com

Bow

el C

ance

rs

[137] HDL Gastric cancer c(Normal-HDL) =150

c(Low-HDL) = 34

In the low serum HDL group, lymphatic and vascular invasion was significantly increased in comparison to the normal serum HDL group.

[138] Chl Colon cancer c = 691 Low serum Chl levels were found to be associated with high incidence of cancer.

[139] Chl Colorectal cancer n = 85

c = 85

Serum Chl levels were significantly lower for the colorectal cancer group than for the control group.

[140] TGs, HDL, LDL, apoA-1 and apoB

Colorectal adenoma c(With colorectal adenomas)=5,958

c( non-advanced adenomas) =5,504

c (With advanced adenomas) = 454

Higher levels of serum TG were significantly associa-ted with increased prevalence of both advanced and non-advanced colorectal adenomas. Higher levels of serum apoA-1 and HDL were also significantly associated with increased prevalence of non-advan-ced adenomas.

[141] Chl Colorectal adenoma c = 842 Serum Chl levels were significantly higher and po-sitively associated with the incidence of colorectal adenoma.

[142] Chl, HDL and TGs Colorectal adenoma n = 2,120

c(Tubular adenoma) = 333

c(Villous-rich tubulovillous/villous

adenoma) =53

Higher serum TG levels were associated with high risk of tubulovillous/villous adenoma in rectosig-moid colon as compared to the control group.

Pros

tate

Can

cers

[143] α-linolenic acid Prostate cancer n = 120

c = 120

Lower α-linolenic acid levels in plasma were associ-ated with reduced risk of prostate cancer as compa-red to the controls.

[144] Chl, LDL, HDL, TGs, apo A-1 and apo B

Newly diagnosed and untreated Prostate cancer

c(without metastasis) = 73

c(with metastasis) = 30

Reduced serum Chl levels and faster clearance of LDL were observed in prostate cancer patients. No difference was observed in HDL, TGs and apoA-1 and B levels in cancer patients as compared to the controls.

[145] Chl, TGs, HDL, LDL, apo A-I, A-II, E and Lp(a)

Estrogen treated Prostate cancer

c = 15 Estrogen treatment induced a significant increase in serum TG, HDL and apolipoproteins A-I and A-II levels in prostate cancer patients. Moreover, LDL, apolipoprotein E and Lp(a) decreased in patients after estrogen treatment.

Lung

Can

cers

[146] HDL Lung cancer N/A Significantly lower levels of serum HDL were detec-ted in patients in comparison to controls.

[147] HDL Squamous cell and small cell lung cancer

c = 135

n = N/A

All lung cancer patients had significantly lower ser-um HDL levels than the controls.

[148] Chland TGs Squamous cell and small cell lung cancer

n = 39

c = 135

Low serum Chl levels were observed in all lung can-cer patients in comparison to the controls. Whereas low serum TG levels were observed only in squa-mous cell lung cancer patients when compared to the controls.

[149] LDL Small cell lung cancer

n = 39

c = 34

There was no statistically significant difference in serum LDL levels between small cell lung cancer patients and the controls.

Live

r ca

ncer

s

[150] LDL Liver cancer N =16,217 Low serum LDL levels were associated with eleva-ted risk of liver cancer mortality.

Hea

d an

d N

eck

Canc

ers

[151] Chl, TGs, LDL and Chl:HDL

Oral squamous cell carcinoma

n = 20

c = 30

Significantly lower serum Chl and TG levels were observed in cancer patients in comparison to the controls.

[152] HDL, LDL, Chl and VLDL

Oral cancer and leu-koplakia

n = 30

c = 30

Significantly decreased serum Chl, HDL, and LDL le-vels were observed in cancer patients in comparison to the controls.

[153] Chl, HDL, VLDL and TGs

Oral cancer (OC) and

Oral pre-cancer (OPC)

n = 70

c(OC) = 70

c(OPC) = 70

Significantly lower serum Chl, HDL, VLDL, and TGs were observed in OC group in comparison to the controls. In the OPC group significant decrease in Chl and HDL was also observed.

[154] Chl, HDL, TGs and VLDL

Untreated Head and neck cancer and OPC

n = 52

c = 184

c (OPC) = 153

Significantly lower plasma Chl and HDL levels were observed in cancer and OPC patients in comparison to the controls. VLDL and TG levels were signifi-cantly lower in cancer patients as compared to the patients with OPC and controls.

Hem

atop

oiet

ic C

ance

rs

[155] Chl, HDL, LDL,VLDL and TGs

Acute leukemia and non-Hodgkin’s lymphoma

c =25 Extremely low levels of plasma HDL, while, elevated levels of plasma TG and VLDL were observed in the cancer patients.

[156] Chl, HDL, LDL, VLDL, TGs, apo A-1, B andLp (a)

Acute lymphocytic leukemia (ALL) patients before and after induction therapy

c =10 Before treatment (at diagnosis) lower serum Chl and HDL levels were observed in the cancer patients. Ho-wever, after induction treatment significant increase in HDL and apo A-1 values was observed only in the patients that achieved complete remission.

[157] Chl, TGs, HDL, LDL,-VLDL, apo A1, apo B, and Lp (a)

Childhood ALL n =15

c(ALL at diagnosis) = 24

c(During consolidation therapy with

L-asparaginase) = 16

c(During maintenance therapy without

L-asparaginase) = 18

c(Children previously

treated for leukemia) = 15

c(Children with other forms

of cancer) = 17

Before treatment (at diagnosis) lower serum HDL, ApoA1 and Lp(a) levels were observed in the cancer patients in comparison to the controls. Significantly reduced HDL and apoA1 were observed in children with widespread but not localized solid tumors. During combination therapy with L-asparaginase extremely elevated TGs and a striking reduction in Lp(a) levels were observed. However, it was not the case during combination therapy without L-asparaginase or in children during treatment for solid tumors.

[158] Chl, HDL, TGs, LDL, VLDL and apo B

Acute non-lym-phocytic leukemia (ANLL) and ALL

c (ANLL) = 25

c (ALL) = 18

Before treatment (at diagnosis) lower serum Chl, LDL, HDL, VLDL and TG levels were observed in the ANLL patients. However, in ALL patients’ serum TG and VLDL levels at diagnosis were significantly higher than in the normal population. After effective chemotherapy significant increase in Chl, LDL and apo B was observed.

[159] Chl, TGs, HDL andLDL Acute leukemia before and after chemotherapy

c = 78 Serum Chl, LDL and HDL levels were significantly lower before chemotherapy than after; whereas TG levels were higher before therapy than after.

Brea

st &

Ova

rian

Can

cers

[160] Chl, HDL, LDL and TGs Breast cancer c = 83 Significantly higher serum TG levels and significant-ly lower serum Chl and HDL levels were observed in patients as compared to the patients with less advanced disease and controls.

However, lower serum LDL levels were observed in patients with bony metastasis as compared to the patients with liver or liver plus bony metastasis and controls.

[161] Phospholipids, TGs, Chl, HDL and Free fatty acids

Breast cancer n = 50

c = 48

Higher plasma levels of lipids, phospholipids, TG, Chl and free fatty acids were observed in cancer patients in comparison to the control subjects. However, HDL levels were significantly lower in these patients.

[162] Chl and TGs Breast cancer n =13

c(Without metabolic syndrome) = 23

There was no significant difference in serum Chl and TG levels between cancer patients and the control subjects.

[163] Chl, LDL and HDL Untreated Breast and Epithelial Ovarian cancer

n = 30

c (Breast Cancer) = 17

c (Ovarian Cancer) = 15

Higher serum levels of Chl and LDL were observed in breast cancer patients in comparison to the control subjects. However, HDL levels were not different in these patients when compared to controls.

There was no significant difference in Chl, LDL or HDL serum levels between ovarian cancer patients and controls.

[164] n6-PUFA and n3-PUFA


c = 87

Low serum n6-PUFA linoleic acid levels indicated higher risk of cancer.

No significant association between cancer risk and serum n3-PUFA was observed.



www.avidscience.com

Abbreviations: Chl, cholesterol; TGs, triglycerides; HDL, high density lipoprotein cholesterol; LDL, low density li-poprotein cholesterol; VLDL, very low density lipoprotein cholesterol; apo, apolipoprotein; Lp, lipoprotein; PUFA, Polyunsaturated fatty acid; CMF, combination of cyclo-phosphamidmethotroxate and 5-fluorouracil; N, total population studied; n, number of controls; c, number of patients; N/A, not available; OPC, oral precancerous con-

ditions.

[165] Chl, LDL, VLDL, HDL, TGs and Free fatty acids

Adjuvant tamoxifen treated Breast cancer

c = 45 Plasma levels of total Chl, free Chl and LDL were si-gnificantly lower in patients after tamoxifen therapy (at 3 and 6 months’ evaluation); whereas plasma levels of TG, VLDL, HDL and free fatty acids were significantly higher.

[166] HDL Breast cancer N = 7,575 Low plasma HDL levels among premenopausal women might be a marker of increased breast cancer risk.

[167] Chl, HDL, LDL, VLDL, HDL:LDL andChl:HDL ratio

Untreated Breast cancer patients

n = 50

c = 100

Significantly high serum levels of Chl, LDL, HDL: LDL and Chl:HDL were observed in patients as compared to the control subjects. However, HDL and VLDL le-vels were not significantly different between these two groups.

[168] Chland TGs Advanced Breast cancer

c = 65 Higher serum levels of TG and Chl could indicate progression or recurrence of breast cancer.

[169] Chl, HDL, LDL and TGs Breast cancer n = 105

c = 58

Higher plasma TG levels were observed in the pati-ents as compared to the controls.

There was no statistically significant difference ob-served in Chl, HDL and LDL between the patients and controls.

[170] Chl, TGs, LDL and LDL:HDL

Breast cancer c = 324 Higher levels of serum Chl, TG, LDL and LDL:HDL were associated with high risk of cancer.

[171] Chl, HDL, LDL, VLDL and Chl:HDL


c = 120

Higher serum levels of Chl, LDL, and Chl:HDL were observed in the patients as compared to the con-trols.

No statistically significant difference was observed in HDL and VLDL levels between the patients and the controls.

[172] Chl Breast cancer N = 79,994 Serum Chl levels were not associated with breast cancer risk in postmenopausal women.

[173] HDL Breast cancer N = 206 Low serum HDL levels could serve as an additional biomarker of breast cancer risk.

[174] Chl and TGs Breast cancer c = 520 Higher serum Chl levels were associated with breast cancer recurrence; whereas serum TG levels were not associated with breast cancer risk.

[175] Chl, TGs, HDL and LDL

Breast cancer N = 31,209 No association between breast cancer risk and ser-um lipids was found in this study.

[176] Chl, HDL, LDL and TGs

Breast cancer c = 310 Plasma TG levels were significantly higher in preme-nopausal breast cancer patients.

[177] HDL Breast cancer N = 38,823 Low serum HDL level is associated with increased postmenopausal cancer risk.

[178] Chl Ductal carcinoma in situ (DCIS) of the breast

c (DCIS) = 152

c (With benign surgical conditions)= 242

There was no statistically significant difference of the serum Chl levels in the patients of DCIS as compared to the patients with benign surgical con-ditions. However, an elevated risk was observed for DCIS in postmenopausal versus premenopausal women, and in peri-menopausal versus premeno-pausal women.

[179] HDL Breast cancer n = 329

c = 307

Higher HDL levels were observed as a marker of breast cancer risk.

[180] TGs, HDL and apo A1:HDL

Newly diagnosed untreated Breast cancer

n = 30

c = 30

An increase in plasma TG levels and apo A1: HDL and a decrease in plasma HDL levels, especially in the HDL-2 subfraction, were observed in the patients with cancer as compared to the controls.

[181] Chl, HDL, LDL and TGs Breast cancer n = 60

c = 60

There was a significant increase in serum Chl, TG and LDL levels in the patients as compared to the controls while HDL remained unchanged.

[182] Chl and β-lipo-proteins

Breast cancer N = 46,570 Low serum Chl and high β-lipoproteins levels were associated with high risk of cancer.

[183] HDL Breast cancer n = 1,380

c = 690

Low serum HDL levels were associated with high risk of cancer among premenopausal women.

[184] Chl Breast cancer N = 24,329 High serum Chl levels were associated with increa-sed risk of cancer.

[185] Chl, HDL, LDL and TGs Breast cancer N = 5,207 Low levels of serum HDL were associated with increased risk of cancer. Elevated serum TG levels may be associated with high risk of cancer but the trend was not significant. There was no relationship between serum Chl or LDL levels and risk of cancer.

[186] Chl, TGs, HDL and Chl:HDL

Breast cancer and Pancreatic cancer

n = 44

c (Breast cancer) = 56

c (Pancreatic cancer) = 32

An increase in serum TG and a decrease in HDL levels especially in the HDL-2 subfraction, were observed in the cancer patients as compared to the controls. Breast cancer patients had significantly higher Chl: HDL as compared to the controls and the patients with pancreatic cancer.

[187] Chl, LDL, HDL, VLDL and TGs

Breast Cancer n = 154

c (With early stage) = 249

High serum levels of TG, LDL and VLDL were associ-ated with high risk of cancer.

[188] Chl, TGs, HDL and LDL

Untreated Breast Cancer

n = 42

c = 54

Plasma Chl, LDL and TG levels were found to be sig-nificantly elevated among cancer patients as compa-red to the controls. However, significantly decreased plasma HDL levels were observed in the patients than in the controls.

[189] Chl, HDL, TGs, LDL, apo-B, and apoA-I

Breast and Ovarian cancer

N = 234,494

c (Breast cancer) = 6,105

c (ovarian cancer) = 808

Low serum Chl, and apo-B levels might be associated with high risk of breast cancer. However, low levels of serum HDL were associated with increased risk of ovarian cancer.

No otherassociationsbetween other lipid compo-nents and risk of breast cancer or ovarian cancer showed statistical significance.

[125] Chl, LDL, TGs and a-lipoproteins


c = 103

Increased serum total Chl, free Chl, LDL, TG and a-li-poprotein levels were observed in cancer patients as compared to non-cancer patients.

Endo

met

rial

Ca

ncer

s

[190] Chl, TGs, HDL and LDL Endometrial Cancer N = 31,473 High serum TG levels were associated with high risk of cancer.

There was no association between Chl, LDL and HDL and endometrial cancer risk.

[191] TGs, Chl,

HDL, LDL, TGs:HDL, apo A-I and apo-B

Endometrial cancer N = 225,432 Elevated serum levels of Chl, TG and TG:HDL were associated with high risk of cancer but no asso-ciation was found for the other lipid components studied.



www.avidscience.com

Table 2: Association between plasma lipids and risk of he-matological cancers: Overview of the data obtained from

different prospective-cohort studies.

References1. Allampallam K, Dutt D, Nair C, Shetty V, Mundle

S. The clinical and biologic significance of abnor-mal lipid profiles in patients with myelodysplastic syndromes. J Hematother Stem Cell Res. 2000; 9: 247-255.

2. Patel PS, Shah MH, Jha FP, Raval GN, Rawal RM, et al. Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous con-ditions. Indian J Cancer. 2004; 41: 25-31.

3. Halton JM, Nazir DJ, McQueen MJ, Barr RD. Blood lipid profiles in children with acute lymph-oblastic leukemia. Cancer. 1998; 83: 379-384.

4. Muntoni S, Atzori L, Mereu R, Satta G, Macis MD, et al. Serum lipoproteins and cancer. Nutr Metab Cardiovasc Dis. 2009; 19: 218-225.

5. Usman H, Rashid R, Ameer F, Iqbal A, Zaid M. Revisiting the dyslipidemia associated with acute leukemia. Clin Chim Acta. 2015; 444: 43-49.

6. Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell. 2008; 134: 703-707.

7. Swinnen JV, K Brusselmans, G Verhoeven. In-creased lipogenesis in cancer cells: new players, novel targets. Current Opinion in Clinical Nutri-tion & Metabolic Care. 2006; 9: 358-365.

Follow-up Period

Sample Size(n)

Major Findings References

1990-2004 n =33,368 No association was observed between total serum cholesterol levels and the risk of leu-kemia.

[127]

1971-1984 n = 12488 Inverse association between total serum cholesterol levels and risk of leukemia was observed.

[192]

1985-2003 n = 172210 Risk of hematopoietic cancer was significant-ly decreased for participants in the highest total serum cholesterol tertile (>235.0 mg/dl in men and >229.0 mg/dl in women). Ho-wever, this association was short-term and was only observed for the malignancies diag-nosed within 5 months of plasma cholesterol assessments. For the malignances that were diagnosed after 5 months cancer risk was not significantly associated with total serum cholesterol.

[131]

1972-2005 n = 577330 Inverse association between total serum cho-lesterol levels and hematopoietic cancers was observed.

[124]

1995-2005 n = 6107 In type 2 diabetes patients the association between LDL and leukemia was V-shaped, whereby both low and high levels of LDL were associated with elevated risk of cancer

[193]

1985-2003 n = 29,093 Inverse association of total serum cholesterol and HDL-C levels with hematopoietic cancers was observed.

[194]

1968-1980 n = 39,268 Statistically significant inverse association between total serum cholesterol levels and leukemia was observed during the first years of follow-up, especially for rapidly developing cancers. However, in female participants this association was weaker in comparison to the male counterparts.

[195]

1960-1976 n = 3102 Statistically significant inverse association between total serum cholesterol levels and leukemia was observed. However, in female participants this association was weaker in comparison to the male counterparts.

[196]

1965-1968 n = 7716 No significant association was observed bet-ween total serum cholesterol levels and the risk of leukemia.

[197]



www.avidscience.com

8. Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 2007; 7: 763-777.

9. Alexopoulos CG, Pournaras S, Vaslamatzis M, Avgerinos A, Raptis S. Changes in serum lipids and lipoproteins in cancer patients during chemo-therapy. Cancer Chemother Pharmacol. 1992; 30: 412-416.

10. Woditschka S, Habel LA, Udaltsova N, Friedman GD, Sieh W. Lipophilic statin use and risk of breast cancer subtypes. Cancer Epidemiol Biomarkers Prev. 2010; 19: 2479-2487.

11. Munir R, Usman H, Hasnain S, Smans K, Kalbach-er H, et al. A typical plasma lipid profile in cancer patients: Cause or consequence? Biochimie. 2014; 102: 9-18.

12. Llaverias G, Danilo C, Mercier I, Daumer K, Ca-pozza F. Role of cholesterol in the development and progression of breast cancer. Am J Pathol. 2011; 178: 402-412.

13. Shimizu H, Ross RK, Bernstein L, Yatani R, Hen-derson BE. Cancers of the prostate and breast among Japanese and white immigrants in Los An-geles County. Br J Cancer. 1991; 63: 963-966.

14. Suburu J, Chen YQ. Lipids and prostate cancer. Prostaglandins Other Lipid Mediat. 2012; 98:

1-10.

15. Yoon Jung Yang, Seon Hwa Lee, Sung Joon Hong, Bong Chul Chung. Comparison of fatty acid pro-files in the serum of patients with prostate cancer and benign prostatic hyperplasia. Clinical bio-chemistry. 1999; 32: 405-409.

16. Rao CV, Hirose Y, Indranie C, Reddy BS. Modula-tion of experimental colon tumorigenesis by types and amounts of dietary fatty acids. Cancer Res. 2001; 61: 1927-1933.

17. Agnoli C, Grioni S, Sieri S, Sacerdote C, Vineis P5. Colorectal cancer risk and dyslipidemia: a case-cohort study nested in an Italian multicentre co-hort. Cancer Epidemiol. 2014; 38: 144-151.

18. Wulaningsih W, Garmo H, Holmberg L, Hammar N, Jungner I. Serum Lipids and the Risk of Gas-trointestinal Malignancies in the Swedish AMOR-IS Study. J Cancer Epidemiol. 2012; 2012: 792034.

19. Kitahara CM, Berrington de González A, Freed-man ND, Huxley R, Mok Y. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol. 2011; 29: 1592-1598.

20. Törnberg SA, Holm LE, Carstensen JM, Eklund GA. Risks of cancer of the colon and rectum in re-lation to serum cholesterol and beta-lipoprotein. N Engl J Med. 1986; 315: 1629-1633.



www.avidscience.com

21. McKeown-Eyssen G. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epi-demiol Biomarkers Prev. 1994; 3: 687-695.

22. Rose G, Blackburn H, Keys A, Taylor HL, Kannel WB. Colon cancer and blood-cholesterol. Lancet. 1974; 1: 181-183.

23. Sidney S, Farquhar JW. Cholesterol, cancer, and public health policy. Am J Med. 1983; 75: 494-508.

24. Williams RR, Sorlie PD, Feinleib M, McNamara PM, Kannel WB. Cancer incidence by levels of cholesterol. JAMA. 1981; 245: 247-252.

25. Kagan A, McGee DL, Yano K, Rhoads GG, Nomu-ra A. Serum cholesterol and mortality in a Japa-nese-American population: the Honolulu Heart program. Am J Epidemiol. 1981; 114: 11-20.

26. Ghahremanfard F, Mirmohammadkhani M, Shahnazari B, Gholami G, Mehdizadeh J. The Valuable Role of Measuring Serum Lipid Profile in Cancer Progression. Oman Med J. 2015; 30: 353-357.

27. Schatzkin A, Hoover RN, Taylor PR, Ziegler RG, Carter CL. Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I Epi-demiologic Follow-up Study. Cancer Res. 1988;

48: 452-458.

28. Iso H, Ikeda A, Inoue M, Sato S, Tsugane S; JPHC Study Group. Serum cholesterol levels in relation to the incidence of cancer: the JPHC study co-horts. Int J Cancer. 2009; 125: 2679-2686.

29. Ahn J, Lim U, Weinstein SJ, Schatzkin A, Hayes RB. Prediagnostic total and high-density lipopro-tein cholesterol and risk of cancer. Cancer Epide-miol Biomarkers Prev. 2009; 18: 2814-2821.

30. Hiatt RA, Fireman BH. Serum cholesterol and the incidence of cancer in a large cohort. J Chronic Dis. 1986; 39: 861-870.

31. Chung YW, Han DS, Park YK, Son BK, Paik CH. Association of obesity, serum glucose and lipids with the risk of advanced colorectal adenoma and cancer: a case-control study in Korea. Dig Liver Dis. 2006; 38: 668-672.

32. Law MR, Thompson SG. Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control. 1991; 2: 253-261.

33. Borena W, Stocks T, Jonsson H, Strohmaier S, Nagel G. Serum triglycerides and cancer risk in the metabolic syndrome and cancer (Me-Can) collaborative study. Cancer Causes Control. 2011; 22: 291-299.



www.avidscience.com

34. Tulinius H, Sigfússon N, Sigvaldason H, Bjarna-dóttir K, Tryggvadóttir L. Risk factors for malig-nant diseases: a cohort study on a population of 22,946 Icelanders. Cancer Epidemiol Biomarkers Prev. 1997; 6: 863-873.

35. Ulmer H, Borena W, Rapp K, Klenk J, Strasak A. Serum triglyceride concentrations and cancer risk in a large cohort study in Austria. Br J Cancer. 2009; 101: 1202-1206.

36. Aleksandrova K, Boeing H, Jenab M, Bas Bueno-de-Mesquita H, Jansen E. Metabolic syndrome and risks of colon and rectal cancer: the European prospective investigation into cancer and nutri-tion study. Cancer Prev Res (Phila). 2011; 4: 1873-1883.

37. Stocks T, Lukanova A, Bjørge T, Ulmer H, Manjer J. Metabolic factors and the risk of colorectal can-cer in 580,000 men and women in the metabolic syndrome and cancer project (Me-Can). Cancer. 2011; 117: 2398-2407.

38. Tsushima M, Nomura AM, Lee J, Stemmermann GN. Prospective study of the association of serum triglyceride and glucose with colorectal cancer. Dig Dis Sci. 2005; 50: 499-505.

39. Palli D, Berrino F, Vineis P, Tumino R, Panico S. A molecular epidemiology project on diet and can-

cer: the EPIC-Italy Prospective Study. Design and baseline characteristics of participants. Tumori. 2003; 89: 586-593.

40. Souza DR, Nakachima L, Biagioni RB, Nakazone MA, Pinhel MA. Relevance of apolipoprotein E4 for the lipid profile of Brazilian patients with coro-nary artery disease. Braz J Med Biol Res. 2007; 40: 189-197.

41. Shinomiya S, Sasaki J, Kiyohara C, Tsuji E, Inoue H. Apolipoprotein E genotype, serum lipids, and colorectal adenomas in Japanese men. Cancer Lett. 2001; 164: 33-40.

42. Watson MA, Gay L, Stebbings WS, Speakman CT, Bingham SA. Apolipoprotein E gene poly-morphism and colorectal cancer: gender-specific modulation of risk and prognosis. Clin Sci (Lond). 2003; 104: 537-545.

43. Slattery ML, Sweeney C, Murtaugh M, Ma KN, Potter JD. Associations between apoE genotype and colon and rectal cancer. Carcinogenesis. 2005; 26: 1422-1429.

44. Saha SP, Kalathiya RJ, Davenport DL, Ferraris VA, Mullett TW. Survival after Pneumonectomy for Stage III Non-small Cell Lung Cancer. Oman Med J. 2014; 29: 24-27.

45. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating



www.avidscience.com

the world cancer burden: Globocan 2000. Int J Cancer. 2001; 94: 153-156.

46. Levy RI. Cholesterol and disease--what are the facts? JAMA. 1982; 248: 2888-2890.

47. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110: 227-239.

48. Ghadir MR, Riahin AA, Havaspour A, Noora-nipour M, Habibinejad AA. The relationship be-tween lipid profile and severity of liver damage in cirrhotic patients. Hepat Mon. 2010; 10: 285-288.

49. Mehboob F, F Ranjha. Dyslipidemia in Chronic Liver Disease. age. 20: 10.

50. Saito N, Sairenchi T, Irie F, Iso H, Iimura K. Low serum LDL cholesterol levels are associated with elevated mortality from liver cancer in Japan: the Ibaraki Prefectural health study. Tohoku J Exp Med. 2013; 229: 203-211.

51. Sorokin A, Brown JL, Thompson PD. Primary bil-iary cirrhosis, hyperlipidemia, and atherosclerotic risk: a systematic review. Atherosclerosis. 2007; 194: 293-299.

52. Irshad M, Dube R, Joshi YK. Impact of viral hepa-titis on apo- and lipoprotein status in blood. Med

Princ Pract. 2007; 16: 310-314.

53. Jiang JT, Xu N, Zhang XY, Wu CP. Lipids changes in liver cancer. J Zhejiang Univ Sci B. 2007; 8: 398-409.

54. Siagris D, Christofidou M, Theocharis GJ, Pag-oni N, Papadimitriou C. Serum lipid pattern in chronic hepatitis C: histological and virological correlations. J Viral Hepat. 2006; 13: 56-61.

55. Selimoglu MA, Aydogdu S, Yagci RV. Lipid pa-rameters in childhood cirrhosis and chronic liver disease. Pediatr Int. 2002; 44: 400-403.

56. Spósito AC, Vinagre CG, Pandullo FL, Mies S, Raia S. Apolipoprotein and lipid abnormalities in chronic liver failure. Braz J Med Biol Res. 1997; 30: 1287-1290.

57. Cicognani C, Malavolti M, Morselli-Labate AM, Zamboni L, Sama C. Serum lipid and lipopro-tein patterns in patients with liver cirrhosis and chronic active hepatitis. Arch Intern Med. 1997; 157: 792-796.

58. Cimminiello C, Soncini M, Gerosa MC, Toschi V, Motta A, et al. Lipoprotein (a) and fibrinolytic system in liver cirrhosis. Coagulation Abnormali-ties in Liver Cirrhosis (CALC) Study Group. Bi-omed Pharmacother. 1995; 49: 364-368.

59. Ahaneku JE, Taylor GO, Olubuyide IO, Agbedana



www.avidscience.com

EO. Abnormal lipid and lipoprotein patterns in liver cirrhosis with and without hepatocellular carcinoma. J Pak Med Assoc. 1992; 42: 260-263.

60. Cambien F, Ducimetiere P, Richard J. Total serum cholesterol and cancer mortality in a middle-aged male population. Am J Epidemiol. 1980; 112: 388-394.

61. Perales J, Angel Lasunción M, Cano A, Martín-Scapa MA, Matíes M. [Changes in the lipid profile in chronic hepatopathies]. Med Clin (Barc). 1994; 102: 364-368.

62. Halsted CH1. Nutrition and alcoholic liver dis-ease. Semin Liver Dis. 2004; 24: 289-304.

63. Jiang J, Zhang X, Wu C, Qin X, Luo G, et al. In-creased plasma apoM levels in the patients suf-fered from hepatocellular carcinoma and other chronic liver diseases. Lipids Health Dis. 2008; 7: 25.

64. Sherlock S, J Dooley. Assessment of liver function. Disease of the Liver and Biliary System. 9th edn. London: Blackwell Scientific Publications. 1993; 17-32.

65. Cooper ME, Akdeniz A, Hardy KJ. Effects of liver transplantation and resection on lipid parameters: a longitudinal study. Aust N Z J Surg. 1996; 66:

743-746.

66. Motta M, Giugno I, Ruello P, Pistone G, Di Fazio I. Lipoprotein (a) behaviour in patients with hepa-tocellular carcinoma. Minerva Med. 2001; 92: 301-305.

67. Ooi K, Shiraki K, Sakurai Y, Morishita Y, Nobori T. Clinical significance of abnormal lipoprotein patterns in liver diseases. Int J Mol Med. 2005; 15: 655-660.

68. Lewis GF, Rader DJ. New insights into the regula-tion of HDL metabolism and reverse cholesterol transport. Circ Res. 2005; 96: 1221-1232.

69. Heeren J, Grewal T, Laatsch A, Becker N, Rin-ninger F. Impaired recycling of apolipoprotein E4 is associated with intracellular cholesterol accu-mulation. J Biol Chem. 2004; 279: 55483-55492.

70. Kanel GC, Radvan G, Peters RL. High-density li-poprotein cholesterol and liver disease. Hepatol-ogy. 1983; 3: 343-348.

71. Popescu I, Simionescu M, Tulbure D, Sima A, Catana C. Homozygous familial hypercholester-olemia: specific indication for domino liver trans-plantation. Transplantation. 2003; 76: 1345-1350.

72. Malaguarnera M, Trovato G, Restuccia S, Giugno I, Franzé CM. Treatment of nonresectable hepa-



www.avidscience.com

tocellular carcinoma: review of the literature and meta-analysis. Adv Ther. 1994; 11: 303-319.

73. Langstein HN, Norton JA. Mechanisms of cancer cachexia. Hematol Oncol Clin North Am. 1991; 5: 103-123.

74. Tracey KJ, Lowry SF, Cerami A. Cachectin: a hor-mone that triggers acute shock and chronic ca-chexia. J Infect Dis. 1988; 157: 413-420.

75. Gifford GE, ML Lohmann-Matthes. Gamma interferon priming of mouse and human mac-rophages for induction of tumor necrosis factor production by bacterial lipopolysaccharide. J Natl Cancer Inst. 1987; 78: 121-124.

76. Hiraoka H, Yamashita S, Matsuzawa Y, Kubo M, Nozaki S. Decrease of hepatic triglyceride lipase levels and increase of cholesteryl ester transfer protein levels in patients with primary biliary cir-rhosis: relationship to abnormalities in high-den-sity lipoprotein. Hepatology. 1993; 18: 103-110.

77. Samonakis DN, Koutroubakis IE, Sfiridaki A, Malliaraki N, Antoniou P. Hypercoagulable states in patients with hepatocellular carcinoma. Dig Dis Sci. 2004; 49: 854-858.

78. Higuchi K, Hospattankar AV, Law SW, Meglin N, Cortright J. Human apolipoprotein B (apoB) mRNA: identification of two distinct apoB mR-

NAs, an mRNA with the apoB-100 sequence and an apoB mRNA containing a premature in-frame translational stop codon, in both liver and intes-tine. Proc Natl Acad Sci U S A. 1988; 85: 1772-1776.

79. Albers JJ, Adolphson JL, Hazzard WR. Radioim-munoassay of human plasma Lp(a) lipoprotein. J Lipid Res. 1977; 18: 331-338.

80. Basili S, Andreozzi P, Vieri M, Maurelli M, Cara D. Lipoprotein (a) serum levels in patients with hepatocarcinoma. Clin Chim Acta. 1997; 262: 53-60.

81. von Eckardstein A, Huang Y, Assmann G. Physi-ological role and clinical relevance of high-density lipoprotein subclasses. Curr Opin Lipidol. 1994; 5: 404-416.

82. Hirano R, Igarashi O, Kondo K, Itakura H, Mat-sumoto A. Regulation by long-chain fatty acids of the expression of cholesteryl ester transfer protein in HepG2 cells. Lipids. 2001; 36: 401-406.

83. Sviridov D, Fidge N. Pathway of cholesterol efflux from human hepatoma cells. Biochim Biophys Acta. 1995; 1256: 210-220.

84. Genest JJ, McNamara JR, Ordovas JM, Martin-Munley S, Jenner JL. Effect of elective hospitaliza-tion on plasma lipoprotein cholesterol and apoli-



www.avidscience.com

poproteins A-I, B and Lp(a). Am J Cardiol. 1990; 65: 677-679.

85. Eggerman TL, Hoeg JM, Meng MS, Tombragel A, Bojanovski D. Differential tissue-specific expres-sion of human apoA-I and apoA-II. J Lipid Res. 1991; 32: 821-828.

86. Garcia A, Barbaras R, Collet X, Bogyo A, Chap H. High-density lipoprotein 3 receptor-depend-ent endocytosis pathway in a human hepatoma cell line (HepG2). Biochemistry. 1996; 35: 13064-13071.

87. Dugi KA, Vaisman BL, Sakai N, Knapper CL, Meyn SM. Adenovirus-mediated expression of hepatic lipase in LCAT transgenic mice. J Lipid Res. 1997; 38: 1822-1832.

88. Busch SJ, Barnhart RL, Martin GA, Fitzgerald MC, Yates MT. Human hepatic triglyceride lipase expression reduces high density lipoprotein and aortic cholesterol in cholesterol-fed transgenic mice. J Biol Chem. 1994; 269: 16376-16382.

89. Santamarina-Fojo S, Haudenschild C, Amar M. The role of hepatic lipase in lipoprotein metabo-lism and atherosclerosis. Curr Opin Lipidol. 1998; 9: 211-219.

90. Brinton EA. Oral estrogen replacement therapy in postmenopausal women selectively raises lev-

els and production rates of lipoprotein A-I and lowers hepatic lipase activity without lowering the fractional catabolic rate. Arterioscler Thromb Vasc Biol. 1996; 16: 431-440.

91. Tan KC, Shiu SW, Pang RW, Kung AW. Effects of testosterone replacement on HDL subfractions and apolipoprotein A-I containing lipoproteins. Clin Endocrinol (Oxf). 1998; 48: 187-194.

92. Forns X, Ampurdanès S, Llovet JM, Aponte J, Quintó L. Identification of chronic hepatitis C pa-tients without hepatic fibrosis by a simple predic-tive model. Hepatology. 2002; 36: 986-992.

93. Tanaka H, Tsukuma H, Yamano H, Oshima A, Shibata H. Prospective study on the risk of hepa-tocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors, alanine aminotransferase level at dona-tion and interaction with hepatitis B virus. Int J Cancer. 2004; 112: 1075-1080.

94. Shi J, Zhu L, Liu S, Xie WF. A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepa-tocellular carcinoma in China. Br J Cancer. 2005; 92: 607-612.

95. Dessì S, Batetta B, Pulisci D, Spano O, Anchisi C, et al. Cholesterol content in tumor tissues is in-



www.avidscience.com

versely associated with high-density lipoprotein cholesterol in serum in patients with gastrointes-tinal cancer. Cancer. 1994; 73: 253-258.

96. Funahashi T, S Yokoyama, A Yamamoto. Asso-ciation of apolipoprotein E with the low density lipoprotein receptor: demonstration of its co-op-erativity on lipid microemulsion particles. J Bio-chem. 1989; 105: 582-587.

97. Casey PJ, Solski PA, Der CJ, Buss JE. p21ras is modified by a farnesyl isoprenoid. Proc Natl Acad Sci U S A. 1989; 86: 8323-8327.

98. Williams RR, Sorlie PD, Feinleib M, McNamara PM, Kannel WB. Cancer incidence by levels of cholesterol. JAMA. 1981; 245: 247-252.

99. Mulas MF, Abete C, Pulisci D, Pani A, Massidda B. Cholesterol esters as growth regulators of lym-phocytic leukaemia cells. Cell Prolif. 2011; 44: 360-371.

100. Zubaidy AS, AS Aqabi, MHA Maini. Hy-polipoproteinemia as Biological Marker in Acute Leukemia. Iraqi Postgraduate Medical Journal. 2011; 10.

101. Kuliszkiewicz-Janus M, MaÅ‚ecki R, Mo-hamed AS. Lipid changes occuring in the course of hematological cancers. Cell Mol Biol Lett. 2008; 13: 465-474.

102. Naik PP, Ghadge MS, Raste AS. Lipid pro-file in leukemia and Hodgkin’s disease. Indian J Clin Biochem. 2006; 21: 100-102.

103. Baroni S, Scribano D, Pagano L, Zuppi C, Leone G. Lipids and lipoproteins in acute lymph-oblastic leukaemia (ALL). Leuk Res. 1994; 18: 643-644.

104. Scribano D, Baroni S, Pagano L, Zuppi C, Leone G. Return to normal values of lipid pattern after effective chemotherapy in acute lymphoblas-tic leukemia. Haematologica. 1996; 81: 343-345.

105. Kark JD, Smith AH, Hames CG. The rela-tionship of serum cholesterol to the incidence of cancer in Evans County, Georgia. J Chronic Dis. 1980; 33: 311-332.

106. Knekt P, Reunanen A, Aromaa A, Heliövaara M, Hakulinen T. Serum cholesterol and risk of cancer in a cohort of 39,000 men and women. J Clin Epidemiol. 1988; 41: 519-530.

107. Strohmaier S, Edlinger M, Manjer J, Stocks T, Bjørge T. Total serum cholesterol and cancer incidence in the Metabolic syndrome and Cancer Project (Me-Can). PLoS One. 2013; 8: e54242.

108. Iribarren C, Reed DM, Chen R, Yano K, Dwyer JH. Low serum cholesterol and mortality. Which is the cause and which is the effect? Circu-



www.avidscience.com

lation. 1995; 92: 2396-2403.

109. Chyou PH, Nomura AM, Stemmermann GN, Kato I. Prospective study of serum choles-terol and site-specific cancers. J Clin Epidemiol. 1992; 45: 287-292.

110. Rudling M, Gåfvels M, Parini P, Gahrton G, Angelin B.. Lipoprotein receptors in acute my-elogenous leukemia: failure to detect increased low-density lipoprotein (LDL) receptor numbers in cell membranes despite increased cellular LDL degradation. Am J Pathol. 1998; 153: 1923-1935.

111. Vitols S, Norgren S, Juliusson G, Tatidis L, Luthman H. Multilevel regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglu-taryl coenzyme A reductase gene expression in normal and leukemic cells. Blood. 1994; 84: 2689-2698.

112. Gonçalves RP, Rodrigues DG, Maranhão RC. Uptake of high density lipoprotein (HDL) cholesteryl esters by human acute leukemia cells. Leuk Res. 2005; 29: 955-959.

113. Tatidis L, Vitols S, Gruber A, Paul C, Ax-elson M.. Cholesterol catabolism in patients with acute myelogenous leukemia and hypocholester-olemia: suppressed levels of a circulating marker for bile acid synthesis. Cancer Lett. 2001; 170:

169-175.

114. Blackett PR, Koren E, Blackstock R, Downs D, Wang CS. Hyperlipidemia in acute lymphoblas-tic leukemia. Ann Clin Lab Sci. 1984; 14: 123-129.

115. Ray G, Husain SA. Role of lipids, lipopro-teins and vitamins in women with breast cancer. Clin Biochem. 2001; 34: 71-76.

116. Marnett LJ, Tuttle MA. Comparison of the mutagenicities of malondialdehyde and the side products formed during its chemical synthesis. Cancer Res. 1980; 40: 276-282.

117. Delimaris I, Faviou E, Antonakos G, Sta-thopoulou E, Zachari A. Oxidized LDL, serum ox-idizability and serum lipid levels in patients with breast or ovarian cancer. Clin Biochem. 2007; 40: 1129-1134.

118. Yavasoglu I, Tombuloglu M, Kadikoylu G, Donmez A, Cagirgan S. Cholesterol levels in patients with multiple myeloma. Ann Hematol. 2008; 87: 223-228.

119. Scolozzi R, Boccafogli A, Salmi R, Furlani MR, Guidoboni CA. [Hypocholesterolemia in multiple myeloma. Inverse relation to the com-ponent M and the clinical stage]. Minerva Med. 1983; 74: 2359-2364.

120. Lim U, Gayles T, Katki HA, Stolzenberg-



www.avidscience.com

Solomon R, Weinstein SJ. Serum high-density lipoprotein cholesterol and risk of non-hodgkin lymphoma. Cancer Res. 2007; 67: 5569-5574.

121. Idogun SE, Omoti CE. Effects of chemo-therapy on plasma lipids and lipoproteins in Ni-gerian patients with haematological malignancy. Niger Postgrad Med J. 2011; 18: 16-19.

122. Kuliszkiewicz-Janus M, MaÅ‚ecki R, Mo-hamed AS. Lipid changes occuring in the course of hematological cancers. Cell Mol Biol Lett. 2008; 13: 465-474.

123. Hegele RA. Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Gen-et. 2009; 10: 109-121.

124. Strohmaier S, Edlinger M, Manjer J, Stocks T, Bjørge T. Total serum cholesterol and cancer incidence in the Metabolic syndrome and Cancer Project (Me-Can). PLoS One. 2013; 8: e54242.

125. Alexopoulos CG, Blatsios B, Avgerinos A. Serum lipids and lipoprotein disorders in cancer patients. Cancer. 1987; 60: 3065-3070.

126. Simó Camps E, Ortí Llavería A, Sena Fer-rer F, Contreras Barbeta E. [Blood cholesterol in patients with cancer]. An Med Interna. 1998; 15: 363-366.

127. Iso H, Ikeda A, Inoue M, Sato S, Tsugane S;

JPHC Study Group. Serum cholesterol levels in re-lation to the incidence of cancer: the JPHC study cohorts. Int J Cancer. 2009; 125: 2679-2686.

128. Eichholzer M, Stähelin HB, Gutzwiller F, Lüdin E, Bernasconi F. Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Ba-sel study. Am J Clin Nutr. 2000; 71: 569-574.

129. Wallace RB, Rost C, Burmeister LF, Pom-rehn PR. Cancer incidence in humans: relation-ship to plasma lipids and relative weight. J Natl Cancer Inst. 1982; 68: 915-918.

130. Xilin Yang, WingYee So, Gary TC Ko, Ronald CW Ma, Alice PS Kong, et al. Independ-ent associations between low-density lipoprotein cholesterol and cancer among patients with type 2 diabetes mellitus. Canadian Medical Association Journal. 2008; 179: 427-437.

131. Strasak AM, Pfeiffer RM, Brant LJ, Rapp K, Hilbe W. Time-dependent association of total se-rum cholesterol and cancer incidence in a cohort of 172,210 men and women: a prospective 19-year follow-up study. Ann Oncol. 2009; 20: 1113-1120.

132. Alexopoulos CG, Pournaras S, Vaslamatzis M, Avgerinos A, Raptis S, et al. Changes in serum lipids and lipoproteins in cancer patients during



www.avidscience.com

chemotherapy. Cancer Chemother Pharmacol. 1992; 30: 412-416.

133. Raste AS, Naik PP. Clinical significance of lipid profile in cancer patients. Indian J Med Sci. 2000; 54: 435-441.

134. Hiatt RA, Fireman BH. Serum cholesterol and the incidence of cancer in a large cohort. J Chronic Dis. 1986; 39: 861-870.

135. Stähelin HB, Rösel F, Buess E, Brubacher G. Cancer, vitamins, and plasma lipids: prospec-tive Basel study. J Natl Cancer Inst. 1984; 73: 1463-1468.

136. Fiorenza AM, Branchi A, Sommariva D. Serum lipoprotein profile in patients with cancer. A comparison with non-cancer subjects. Int J Clin Lab Res. 2000; 30: 141-145.

137. Tamura T, Inagawa S, Hisakura K, Enomo-to T, Ohkohchi N. Evaluation of serum high den-sity lipoprotein cholesterol levels as a prognostic factor in gastric cancer patients. Journal of Gas-troenterology and Hepatology. 2012; 27: 1635-1640.

138. Williams RR, Sorlie PD, Feinleib M, Mc-Namara PM, Kannel WB. Cancer incidence by levels of cholesterol. JAMA. 1981; 245: 247-252.

139. Forones NM, Falcao JB, Mattos D, Barone

B. Cholesterolemia in colorectal cancer. Hepato-gastroenterology. 1998; 45: 1531-1534.

140. Yang MH, Rampal S, Sung J, Choi YH, Son HJ. The association of serum lipids with colorectal adenomas. Am J Gastroenterol. 2013; 108: 833-841.

141. Mannes GA, Maier A, Thieme C, Wie-becke B, Paumgartner G. Relation between the frequency of colorectal adenoma and the serum cholesterol level. N Engl J Med. 1986; 315: 1634-1638.

142. Sun ZJ, Huang YH, Wu JS, Yang YC, Chang YF. The association of serum lipids with the histo-logical pattern of rectosigmoid adenoma in Tai-wanese adults. BMC Gastroenterol. 2011; 11: 54.

143. Gann PH, Hennekens CH, Sacks FM, Grodstein F, Giovannucci EL. Prospective study of plasma fatty acids and risk of prostate cancer. J Natl Cancer Inst. 1994; 86: 281-286.

144. Henriksson P, Eriksson M, Ericsson S, Rudling M, Stege R. Hypocholesterolaemia and increased elimination of low-density lipoproteins in metastatic cancer of the prostate. Lancet. 1989; 2: 1178-1180.

145. Usui S , Suzuki K , Yamanaka H , Nakano T , Nakajima K, et al. Estrogen treatment of pros-



www.avidscience.com

tate cancer increases triglycerides in lipoproteins as demonstrated by HPLC and immunosepara-tion techniques. Clinica chimica acta. 2002; 317: 133-143.

146. Dessi S, Batetta B, Pulisci D, Spano O, Cherchi R. Altered pattern of lipid metabolism in patients with lung cancer. Oncology. 1992; 49: 436-441.

147. Siemianowicz K, Gminski J, Stajszczyk M, Wojakowski W, Goss M. Serum HDL cholesterol concentration in patients with squamous cell and small cell lung cancer. Int J Mol Med. 2000; 6: 307-311.

148. Siemianowicz K, Gminski J, Stajszczyk M, Wojakowski W, Goss M. Serum total cholesterol and triglycerides levels in patients with lung can-cer. Int J Mol Med. 2000; 5: 201-205.

149. Siemianowicz K, Gminski J, Stajszczyk M, Wojakowski W, Goss M. Serum LDL cholesterol concentration and lipoprotein electrophoresis pattern in patients with small cell lung cancer. Int J Mol Med. 2000; 5: 55-57.

150. Saito N, Sairenchi T, Irie F, Iso H, Iimura K. Low serum LDL cholesterol levels are associated with elevated mortality from liver cancer in Japan: the Ibaraki Prefectural health study. Tohoku J Exp Med. 2013; 229: 203-211.

151. Ghosh G, Jayaram KM, Patil RV, Malik S. Alterations in serum lipid profile patterns in oral squamous cell carcinoma patients. J Contemp Dent Pract. 2011; 12: 451-456.

152. Kumar P, Augustine J, Urs AB, Arora S, Gupta S. Serum lipid profile in oral cancer and leukoplakia: correlation with tobacco abuse and histological grading. J Cancer Res Ther. 2012; 8: 384-388.

153. Lohe VK, Degwekar SS, Bhowate RR, Kadu RP, Dangore SB. Evaluation of correlation of se-rum lipid profile in patients with oral cancer and precancer and its association with tobacco abuse. J Oral Pathol Med. 2010; 39: 141-148.

154. Patel PS, Shah MH, Jha FP, Raval GN, Rawal RM. Alterations in plasma lipid profile pat-terns in head and neck cancer and oral precancer-ous conditions. Indian J Cancer. 2004; 41: 25-31.

155. Spiegel RJ, Schaefer EJ, Magrath IT, Ed-wards BK. Plasma lipid alterations in leukemia and lymphoma. Am J Med. 1982; 72: 775-782.

156. Baroni S, Scribano D, Pagano L, Zuppi C, Leone G. Lipids and lipoproteins in acute lymph-oblastic leukaemia (ALL). Leuk Res. 1994; 18: 643-644.

157. Halton JM, Nazir DJ, McQueen MJ, Barr RD. Blood lipid profiles in children with acute



www.avidscience.com

lymphoblastic leukemia. Cancer. 1998; 83: 379-384.

158. Baroni S, Scribano D, Zuppi C, Pagano L, Leone G. Prognostic relevance of lipoprotein cholesterol levels in acute lymphocytic and non-lymphocytic leukemia. Acta Haematol. 1996; 96: 24-28.

159. Sh A, N Fa. Serum Lipid Profile Alterations in Acute Leukemia Before and After Chemother-apy. Iranian Journal of Blood & Cancer. 2013; 6: 3-9.

160. Knapp ML, S al-Sheibani, PG Riches. Al-terations of serum lipids in breast cancer: effects of disease activity, treatment, and hormonal fac-tors. Clin Chem. 1991; 37: 2093-2101.

161. Bani IA, Williams CM, Boulter PS, Dick-erson JW. Plasma lipids and prolactin in patients with breast cancer. Br J Cancer. 1986; 54: 439-446.

162. Timovska Y, Pivnyuk V, Todor I, Anikusko N, Chekhun V. The spectrum of blood serum li-pids in patients with breast cancer without meta-bolic syndrome. Exp Oncol. 2011; 33: 190-192.

163. Delimaris I, Faviou E, Antonakos G, Sta-thopoulou E, Zachari A. Oxidized LDL, serum ox-idizability and serum lipid levels in patients with breast or ovarian cancer. Clin Biochem. 2007; 40:

1129-1134.

164. Lars J Vatten, KS Bjerve, A Andersen, E Jel-lum. Polyunsaturated fatty acids in serum phos-pholipids and risk of breast cancer: a case-control study from the Janus serum bank in Norway. Eu-ropean Journal of Cancer. 1993; 29: 532-538.

165. Thangaraju M, Kumar K, Gandhirajan R, Sachdanandam P. Effect of tamoxifen on plasma lipids and lipoproteins in postmenopausal women with breast cancer. Cancer. 1994; 73: 659-663.

166. Kucharska-Newton AM, Rosamond WD, Mink PJ, Alberg AJ, Shahar E. HDL-cholesterol and incidence of breast cancer in the ARIC cohort study. Ann Epidemiol. 2008; 18: 671-677.

167. Hasija K, Bagga HK. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women. Indian J Clin Biochem. 2005; 20: 61-66.

168. Zielinski CC, Stuller I, Rausch P, Müller C. Increased serum concentrations of cholesterol and triglycerides in the progression of breast can-cer. J Cancer Res Clin Oncol. 1988; 114: 514-518.

169. Agurs-Collins T, Kim KS, Dunston GM, Adams-Campbell LL. Plasma lipid alterations in African-American women with breast cancer. J Cancer Res Clin Oncol. 1998; 124: 186-190.

170. Liu YL, Qian HX, Qin L, Zhou XJ, Zhang



www.avidscience.com

B. [Association of serum lipid profile with distant metastasis in breast cancer patients]. Zhonghua Zhong Liu Za Zhi. 2012; 34: 129-131.

171. Abdelsalam KE, Hassan IK, Sadig IA. The role of developing breast cancer in alteration of se-rum lipid profile. J Res Med Sci. 2012; 17: 562-565.

172. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE. Serum lipids, lipid-lowering drugs, and the risk of breast cancer. Arch Intern Med. 2005; 165: 2264-2271.

173. Anne-Sofie Furberg, Grazyna Jasienska, Nils Bjurstam, Peter A Torjesen, Aina Emaus, et al. Metabolic and hormonal profiles: HDL choles-terol as a plausible biomarker of breast cancer risk. The Norwegian EBBA Study. Cancer Epidemiol-ogy Biomarkers & Prevention. 2005; 14: 33-40.

174. Bahl M, Ennis M, Tannock IF, Hux JE, Pritchard KI. Serum lipids and outcome of early-stage breast cancer: results of a prospective cohort study. Breast Cancer Res Treat. 2005; 94: 135-144.

175. Gaard M, Tretli S, Urdal P. Risk of breast cancer in relation to blood lipids: a prospective study of 3,209 Norwegian women. Cancer Causes Control. 1994; 5: 501-509.

176. Goodwin PJ, Boyd NF, Hanna W, Hartwick W, Murray D. Elevated levels of plasma triglycer-

ides are associated with histologically defined pre-menopausal breast cancer risk. Nutr Cancer. 1997; 27: 284-292.

177. Furberg AS, Veierød MB, Wilsgaard T, Bernstein L, Thune I. Serum high-density lipo-protein cholesterol, metabolic profile, and breast cancer risk. J Natl Cancer Inst. 2004; 96: 1152-1160.

178. Elkhadrawy TM, Ahsan H, Neugut AI. Se-rum cholesterol and the risk of ductal carcinoma in situ: a case-control study. Eur J Cancer Prev. 1998; 7: 393-396.

179. Ferraroni M, Gerber M, Decarli A, Rich-ardson S, Marubini E. HDL-cholesterol and breast cancer: a joint study in northern Italy and south-ern France. Int J Epidemiol. 1993; 22: 772-780.

180. Schreier LE, Berg GA, Basilio FM, Lopez GI, Etkin AE. Lipoprotein alterations, abdominal fat distribution and breast cancer. Biochem Mol Biol Int. 1999; 47: 681-690.

181. Showkat Ahmad Bhat, Manzoor R Mir, Sabhiya Majid, Ahmad Arif Reshi, Ishraq Husain, et al. Serum Lipid Profile of Breast Cancer Patients in Kashmir. Journal of Investigational Biochemis-try, 2013; 2: 26-31.

182. Törnberg SA, Holm LE, Carstensen JM.



www.avidscience.com

Breast cancer risk in relation to serum cholesterol, serum beta-lipoprotein, height, weight, and blood pressure. Acta Oncol. 1988; 27: 31-37.

183. Kim Y, Park SK, Han W, Kim DH, Hong YC, et al. Serum high-density lipoprotein choles-terol and breast cancer risk by menopausal status, body mass index, and hormonal receptor in Ko-rea. Cancer Epidemiol Biomarkers Prev. 2009; 18: 508-515.

184. Vatten LJ, OP Foss, S Kvinnsland. Overall survival of breast cancer patients in relation to preclinically determined total serum cholesterol, body mass index, height and cigarette smoking: a population-based study. Eur J Cancer. 1991; 27: 641-646.

185. Høyer AP, Engholm G. Serum lipids and breast cancer risk: a cohort study of 5,207 Danish women. Cancer Causes Control. 1992; 3: 403-408.

186. Michalaki V, Koutroulis G, Syrigos K, Piperi C, Kalofoutis A. Evaluation of serum lipids and high-density lipoprotein subfractions (HDL2, HDL3) in postmenopausal patients with breast cancer. Mol Cell Biochem. 2005; 268: 19-24.

187. Laisupasin P, Thompat W, Sukarayodhin S, Sornprom A, Sudjaroen Y. Comparison of Se-rum Lipid Profiles between Normal Controls and Breast Cancer Patients. J Lab Physicians. 2013; 5:

38-41.

188. Ray G, Husain SA. Role of lipids, lipopro-teins and vitamins in women with breast cancer. Clin Biochem. 2001; 34: 71-76.

189. Melvin JC, Seth D, Holmberg L, Garmo H, Hammar N. Lipid profiles and risk of breast and ovarian cancer in the Swedish AMORIS study. Cancer Epidemiol Biomarkers Prev. 2012; 21: 1381-1384.

190. Lindemann K, Vatten LJ, Ellstrøm-Engh M, Eskild A. Serum lipids and endometrial cancer risk: results from the HUNT-II study. Int J Cancer. 2009; 124: 2938-2941.

191. Seth D, Garmo H, Wigertz A, Holmberg L, Hammar N. Lipid profiles and the risk of endo-metrial cancer in the Swedish AMORIS study. Int J Mol Epidemiol Genet. 2012; 3: 122-133.

192. Schatzkin A, Hoover RN, Taylor PR, Zie-gler RG, Carter CL. Site-specific analysis of total serum cholesterol and incident cancer in the Na-tional Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. Cancer Res. 1988; 48: 452-458.

193. Yang X, So W, Ko GT, Ma RC, Kong AP. Independent associations between low-density li-poprotein cholesterol and cancer among patients

60 www.avidscience.com

Advances in Dyslipidemia

with type 2 diabetes mellitus. CMAJ. 2008; 179: 427-437.

194. Ahn J, Lim U, Weinstein SJ, Schatzkin A, Hayes RB. Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer. Cancer Epidemiol Biomarkers Prev. 2009; 18: 2814-2821.

195. Knekt P, Reunanen A, Aromaa A, Heliövaara M, Hakulinen T. Serum cholesterol and risk of cancer in a cohort of 39,000 men and women. J Clin Epidemiol. 1988; 41: 519-530.

196. Kark JD, Smith AH, Hames CG. The rela-tionship of serum cholesterol to the incidence of cancer in Evans County, Georgia. J Chronic Dis. 1980; 33: 311-332.

197. Chyou PH, Nomura AM, Stemmermann GN, Kato I. Prospective study of serum choles-terol and site-specific cancers. J Clin Epidemiol. 1992; 45: 287-292.

chapter 4 abstract cancer associated dyslipidemia€¦ · advances in dyslipidemia advances in...

Documents