changing trends in gastrointestinal disease in the asia–pacific region

179

Journal of Digestive Diseases 2007; 8; 179–185 doi: 10.1111/j.1443-9573.2007.00304.x

Blackwell Publishing AsiaMelbourne, AustraliaCDDChinese Journal of Digestive Diseases1443-9611© 2007 The AuthorsJournal compilation © 2007 Chinese Medical Association Shanghai Branch, ChineseXXXReview ArticleGastrointestinal disease in the Asia–PacificKL Goh

Changing trends in gastrointestinal disease in the Asia–Pacific region

KL GOH

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

The new millennium has seen distinct changes in thepattern of gastrointestinal disease in the Asia–Pacificregion. These changes are important as more than halfof the world’s population come from the region andtherefore impact significantly on the global diseaseburden. The highest incidence of gastric cancer (GCA)has been reported from Asia and GCA remains a veryimportant cancer. However time-trend studies haveshown a decrease in GCA incidence in several countriesin Asia. A rise in cardio-esophageal cancers as seen inthe West has not been reported. On the other hand,colorectal cancer has been steadily increasing in Asiawith age-standardized incidence rates of some countriesapproaching that of the West. The pattern of acid-relateddiseases has also changed. Gastroesophageal refluxdisease is a fast emerging disease with an increasingprevalence of reflux esophagitis and reflux symptoms.

The prevalence of peptic ulcer disease has at the sametime declined in step with a decrease in H. pylori infec-tion. Many of the changes taking place mirror theWestern experience of several decades ago. Astuteobservation of the epidemiology of emerging diseasescombined with good scientific work will allow aclearer understanding of the key processes underlyingthese changes. With rapid modernization, lifestylechanges have been blamed for an increase in severaldiseases including gastroesophageal reflux disease,nonalcoholic fatty liver disease and colorectal cancer.A worrying trend has been the increase in obesityamong Asians, which has been associated with anincrease in metabolic diseases and various gastro-intestinal cancers. Conversely, an improvement in livingconditions has been closely linked to the decrease inGCA and H. pylori prevalence.

KEY WORDS: colorectal cancer, gastric cancer, gastroesophageal reflux disease, Helicobacter pylori, peptic ulcerdisease, time trends.

INTRODUCTION

More than half the world’s population or approxi-mately 4 billion people live in Asia. Changes in trendsof disease in Asia would therefore impact significantlyon the global heath burden. Major changes in disease

and health is inevitable in the Asia–Pacific region as aresult of dramatic socio-economic changes in the regionand concomitant lifestyle changes.

For all diseases, an increased prevalence could be dueto better diagnosis as well as a true increase in thefrequency of disease. Observations of a decrease indisease prevalence are interesting and important aswell. The changing epidemiology of a disease oftenprovides valuable insights as to possible pathogenicmechanisms and the changing epidemiology in Asiaallows us an opportunity to make such observations.

The purpose of this review is to study and summarizethe changes that have taken place in the epidemiologyof major gastrointestinal diseases: gastric cancer (GCA)and colorectal cancer (CRC), as well as that of acid-peptic

Correspondence to: KL Goh, Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur. Malaysia. Email: [email protected]

This article is a write-up of a State of the Art Lecture presented by Professor KL Goh at the Asian Pacific Digestive Week 2005, held in Seoul, Korea from 25th–28th September 2005

2007 The AuthorJournal compilation 2007 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology and Blackwell Publishing Asia Pty Ltd.

180 KL Goh Journal of Digestive Diseases 2007; 8; 179–185


diseases, including peptic ulcer disease (PUD) andgastroesophageal reflux disease (GERD) based onpublished data in the Asia–Pacific region.

GASTRIC CANCER

Gastric cancer remains one of the most common cancersin the Asia–Pacific region. In 2002, two Asia–Pacificcountries, Korea and Japan, recorded the highest gastriccancer incidence in the world for both men andwomen.1 In absolute numbers, for the same year, closeto 1 million new cases of GCA were diagnosed, morethan half the cases were from East Asia, 41% fromChina and 11% from Japan. However Asia is a diversecontinent and incidence rates vary greatly from coun-try to country as well as between ethnic groups. Agestandardized incidence rates in India, Thailand andthe Philippines are among the lowest in the world andrange from 10 to 15 per 100 000 per year.2 In multiracialSingapore, Chinese have the highest incidence ratescompared to low incidence rates among Malays andIndians.2 Similarly in a case-control study from Malay-sia, Chinese race was identified as a significant inde-pendent predictive factor for GCA.3

Food has been often implicated as cause of the highGCA incidence rates among Chinese, Koreans andJapanese. High salt content of oriental foods and theintake of preserved foods such as soya-bean paste soupand Kim-chi among Japanese and Koreans have beenimplicated as a cause.4–6 On the other hand, Indiansappear to be protected because of the high intake ofcurries and chillies, which may contain gastro-protectivefactors such as curcurmin.7,8 Ultimately, causation ofdisease would depend on the interaction between hostgenetic factors and environmental factors includingdiet and H. pylori infection.

Broadly, ecologic comparison studies in Asian popula-tions have shown a close association between H. pyloriinfection and GCA.9 Some anomalies exist. There is ahigh prevalence of H. pylori among both Chinese andIndians in a multiracial Asian population in Malaysiabut an inordinately low GCA incidence among thelatter has been observed and has been called the‘Indian’ enigma.3 This fact is reiterated by the wellreported high prevalence of H. pylori in the Indianpopulation and the relatively low cancer incidencenoted in Indian cancer registries.10,2

While the burden of GCA remains high in the Asia–Pacific region, age-standardized incidence rates (ASR)have started to show a decline. ASR from cancer regis-tries in Osaka, Japan, Qidong county, China and

Singapore for example, show a steady decline over thepast 20 years (Fig. 1).11 Cancer statistics collected fromthe urban districts of Shanghai by the Shanghai CancerInstitute, showed a marked decline in ASR in menfrom 62 to 35.8 and in women from 23.9 to 17.5 per100 000 population from 1979 to 1999.12,13 This is inkeeping with observed trends noted in Western countrieswhere GCA has been observed to have declined sincethe 1940s (Fig. 1).14

This decline is thought to be due to the decreasedintake of salt and food preservatives following thewidespread use of refrigeration of food in the West.Refrigeration has allowed greater intake of fresh fruitsand vegetables with a higher level of antioxidants.15,16

This has been well shown in a study by Fei and Xiaofrom Shanghai where consumption of fresh fruits andvegetables and availability of home refrigeration wasassociated with a lower incidence of gastric cancer.17

H. pylori has now been identified as a critical factor ingastric carcinogenesis.18 With increasing awareness,diagnosis and treatment of the infection, prevalencerates of H. pylori have now also decreased throughoutthe world.19–21 However the decline in GCA precededthe discovery of H. pylori. Paradoxically, the prevalenceof H. pylori, may in fact have also started to declinebefore its discovery. H. pylori is a marker of socioeco-nomic status and improvement in status with betterpersonal and community hygiene has probably been amore important factor in the decrease in the prevalenceof infection.22

Another important change with regard to GCA hasbeen the change in the topography of GCA in Westernpatients which was first noted in the early 1990s.Cardia cancer has been reported to be the fastest growinggastrointestinal cancer in the West.23 However, such achange has not been noted in Asian countries wheredistally located tumors still predominate (Fig. 2).24,25

Although incidence rates of GCA have declined, greaterlife expectancy and an increase in the elderly popula-tion, as is seen in Japan, would mean that the healthburden in terms of actual numbers of GCA patientswould remain the same or even increase.26

COLORECTAL CANCER

Colorectal cancer has long been considered a Westerndisease. There has however, been clear evidence thatCRC incidence rates have been increasing in Asians.11

In the recent Globocan figures of 2002, ASR rates ofCRC have increased markedly in Japan and among

Journal of Digestive Diseases 2007; 8; 179–185 Gastrointestinal disease in the Asia–Pacific 181


Singapore Chinese and are reported to be among thehighest in the world.2 In several Asian countries, theASR of colon and rectal cancer has now surpassed thatof GCA.2

This changing epidemiology follows that of the Westwhere CRC had been steadily over the past 40 to 50years (Fig. 3). The increased incidence of CRC could be

due to better detection and diagnosis of the cancer.With widespread availability of better health care servicesin Asia, flexible colonoscopy has become more readilyavailable. However, the continuing rise in CRC ratespoints to a true increase in CRC.27 The reasons arelikely to be similar to those in the West. Rising afflu-ence with an increase in obesity and a decrease in physicalactivity have been implicated in CRC.28–30 On the other

Figure 1. Time trends age-standardized incidence rates of gastric cancer in men from Western and Asian cancer registriesshowing declining incidence rates. Note the low incidence rates among Indians.11

Figure 2. Comparison of subsite distribution of gastric cancer (men and women) from Western and Asian cancer registries.25



hand, the adoption of a westernized diet of higherprotein and fat content has also been implicated asa cause for the increase in incidence.31,32 Withoutquestion, CRC will be the major GI cancer in theregion in the coming years.

Another interesting observation is the anatomical leftto right shift in location of CRC. This has been observedfor many years in the West. Although recent reportsfrom Asia have shown an overwhelming left sidepredominance (Table 1),33 some studies have shown aproximal shift. For example a study from Hong Kong,China has shown an increase in the proportion ofproximal polyps and studies from Korea and Japan

have shown an increase in the proportion of proximaltumors especially among women and in the elderlypopulation (Fig. 4).34–36

ACID-PEPTIC DISEASES

The marked change in the epidemiology of cancersis also seen with the acid-peptic diseases: peptic ulcerdisease and gastroesophageal reflux disease.

Peptic ulcer disease

The decrease in prevalence of peptic ulcer disease hasbeen documented in several studies from the region(Fig. 5).37–39 While the overwhelming majority of

Figure 3. Time trends of age-standardized incidence rates of colorectal cancer in men from Western and Asian cancerregistries showing increasing rates. Note the low incidence rates among Indians.11

Table 1. Distribution of CRC in an Asian population.33 (Reproduced with permission.)

No 1st lesion 2nd lesion 3rd lesion % of total

Rectum 90 0 0 36.3Sigmoid 69 11 0 32.3Descending 25 3 0 11.3Transverse 13 1 1 6.0Ascending 16 2 0 7.3Caecum 15 2 0 6.9Total 228 19 1 –



patients were diagnosed to have associated H. pyloriinfection, one study from Philippines has noted asteady decline in prevalence of H. pylori-associatedulcers.40 Reports on the prevalence of NSAID useand the increase in NSAID-associated ulcers have alsobeen noted.41

Gastroesophageal reflux disease

Gastroesophageal reflux disease has been considereda rare disease in the East previously. Indeed earlierstudies have shown an inordinately low prevalence ofreflux esophagitis.42 Community-based studies havealso shown a low prevalence of reflux symptoms. Thesituation has changed dramatically. More and betterstudies are now available, which have shown pre-valence of reflux esophagitis approaching 20% and

prevalence of reflux symptoms of 10–15%. More severegrades of esophagitis have also been noted althoughBarrett’s esophagus remains uncommon.43

Helicobacter pylori infection

H. pylori underlies several gastrointestinal disordersincluding GCA and peptic ulcer disease. Reports fromAsia have shown a steady decline of H. pylori over theyears.44–47 Studies from Japan have linked the decreasein H. pylori incidence with an increase in GERD.48

OTHER GASTROINTESTINAL DISEASES

Inflammatory bowel disease (IBD): ulcerative colitisand Crohn’s disease have also been thought to be veryuncommon diseases in Asians. Studies from Japan andChina have, however shown marked increases in prev-alence rates as well as absolute numbers of patientswith IBD.49–52 Data from one study from northernIndia show inordinately high rates of ulcerative colitiscomparable to that seen in the West.53 There is nowenough evidence to show that IBD may be the nextemerging GI disease in the Asia–Pacific region.54

DISCUSSION

The epidemiological changes that have taken placeover a relatively short interval of time point to theinfluence of exogenous factors. Broadly, changes tothat result in a more ‘westernized’ lifestyle, havebeen blamed. Such changes that are relevant to ourdiscussion include dietary changes, improved livingconditions and a decrease in physical activity.

A change in diet to one that is rich in fat and proteinhas been implicated in the rise in incidence of CRC aswell as GERD. This process could be brought aboutdirectly by the change in diet or through associatedproblems such as obesity. Dietary change compoundedby a decrease in the level of physical activity has madeobesity the fastest growing problem in the Asia–Pacificregion.55 An epidemic of obesity-associated diseasessuch as ‘fatty liver’ has already been predicted.56

Paradoxically, dietary change has also meant a changeto a better diet – one that contains less salt and preserv-atives. This has been thought to be the single mostimportant factor in the decline in GCA rates. Animprovement in living conditions and better personaland community hygiene has also resulted in the rapiddecrease in the prevalence in H. pylori and as a conse-quence, a decline in the prevalence of associatedgastroduodenal disease: peptic ulcer and GCA. A decrease

Figure 4. Time trends of the proportion (%) of patients= 70 years of age with proximal tumors.36 (Reproduced withpermission.)

Figure 5. Time trends – proportion of patients withduodenal ulcer, esophagitis and H. pylori infection in anendoscopy-based study.39 (Reproduced with permission.)



in H. pylori infection has resulted in a healthier stomachwith an increase in acid producing capacity which willcontribute to the increase in GERD.57 An improvementin hygiene has conversely been implicated in theincrease in IBD in Western populations.58 This mayalso be the case in the Asian population where anincrease in prevalence has already been observed.

An important demographic factor to consider is theincrease in the proportion of population that is elderlyin the Asia–Pacific region. Apart from degenerative dis-eases, cancers including gastrointestinal cancers wouldincrease and patterns of cancer will also change. Higherconsumption of non-steroidal anti-inflammatory drugsin the elderly will result in an increase in gastrointestinalulceration and associated complications particularlygastrointestinal bleeding despite the decrease inH. pylori associated ulcers.

Epidemiological change in disease is inevitable withtime. The challenge for everyone is to identify putativefactors and implement modifiable or remedial actionto prevent the full deleterious effects of such changes.

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changing trends in gastrointestinal disease in the asia–pacific region

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