Epidemiology of Gastric Cancer

Jeongseon Kim

Cancer Epidemiology BranchNational Cancer Center, Korea

Major Cancer Sites in Korea, 2008

Cancer Cases178,816

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Effects of Interleukin-10 Polymorphisms, Smoking, and Helicobacter pylori Infection on the Risk of Noncardia Gastric Cancer

in a Korean Population

(in review)

Figure. Proposed Correa pathway of pathological events in gastric adenocarcinoma (Fox JG & Wang TC. J Clin Inv

2007;117:60-69)

Figure. Cytokine and chemokine balances regulate neoplasticoutcome (Coussens LM, Werb Z. NIH Public Access 2007)

Interleukin-10 (IL-10)

• a multifunctional anti-inflammatory cytokine that downregulates cell-mediated immune responses and cytotoxic inflammatory responses

• Certain polymorphic promoter variants (-1082/-819/-592) of the IL-10 gene are associated with increased IL-10 production.

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Purpose

• Several environmental factors, including tobacco smoking and H. pylori, have been reported to be associated with gastric carcinogenesis.

• In the present study, we investigated the effects of IL-10 genetic variants, cigarette smoking, and H. pylori infection on the risk of noncardia gastric carcinogenesis, which was stratified by histological type.

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Table 1. Characteristics of Study Subjects

Gastric Cancer Cases

(n=495)

Controls

(n=495)P-value

Age (years), mean ± SD 54.9±8.4 54.3±7.4 0.208

Male, n(%) 337 (68.1) 337 (68.1) 1.000

Family history of gastric cancer, n (%) 220 (44.4) 225 (45.5) 0.749

Smoking status, n (%)

Non-smoker 183 (37.0) 208 (42.0) <0.001

Past-smoker 108 (21.8) 158 (31.9)

Current-smoker 204 (41.2) 129 (26.1)

Alcohol consumption, n (%)

Non-drinker 167 (33.8) 147 (29.7) 0.027

Past-drinker 50 (10.1) 33 (6.7)

Current-drinker 277 (56.1) 315 (63.6)

H. pylori infection (positive), n (%) 443 (89.9) 329 (66.6) <0.001

Income, n (%)

Low 205 (41.4) 165 (33.3) 0.017

Medium 242 (48.9) 286 (57.8)

High 48 (9.7) 44 (8.9)

Education (years), n (%)

<12 231 (46.7) 145 (29.3) <0.001

≥12 264 (53.3) 350 (70.7)

IL-10-1082, n (%)

AA 416 (84.0) 435 (87.9) 0.198

AG 72 (14.6) 56 (11.3)

GG 7 (1.4) 4 (0.8)

IL-10-819, n (%)

TT 231 (46.7) 248 (50.1) 0.325

CT 214 (43.2) 191 (38.6)

CC 50 (10.1) 56 (11.3)

IL-10-592, n (%)

AA 231 (46.7) 248 (50.1) 0.325

CA 214 (43.2) 191 (38.6)

CC 50 (10.1) 56 (11.3)

Histological type of gastric cancer, n (%)

Intestinal 253 (51.1)

Diffuse 214 (43.2)

Mixed 28 (5.7)

Stage of gastric cancer, n (%)

Early gastric cancer 279 (56.4)

Advanced gastric cancer 216 (43.6)

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Table 2. The Association between IL-10 Genetic Variants and the Risk of Gastric Cancer, Stratified by Histologic type of gastric

cancer

*adjusted for age, sex, H. pylori infection and smoking

All Intestinal type (n=253) Diffuse type (n=214)

No. of

Controls (%)

No. of

Cases (%)

Crude

OR (95% CI)

Multivariate OR

(95% CI)a

No. of

Cases (%)

Crude

OR (95% CI)

Multivariate OR

(95% CI) a

No. of

Cases (%)

Crude

OR (95% CI)

Multivariate OR

(95% CI) a

IL-10-1082

AA 435 (87.9) 416 (84.0) 1.0 1.0 209 (82.6) 1.0 1.0 182 (85.1) 1.0 1.0

G carrier 60 (12.1) 79 (16.0) 1.38 (0.96, 1.98) 1.32 (0.90, 1.93)44 (17.4) 1.53 (1.00, 2.33) 1.56 (0.99, 2.45) 32 (14.9) 1.30 (0.80, 2.03) 1.11 (0.68, 1.82)

IL-10-592

AA 248 (50.1) 231 (46.7) 1.0 (Ref) 1.0 107 (42.29) 1.0 1.0 102 (47.7) 1.0 1.0

C carrier 247 (49.9) 264 (53.3) 1.15 (0.89, 1.47) 1.18 (0.91, 1.54) 146 (57.71) 1.37 (1.01, 1.86) 1.50 (1.08, 2.08) 112 (52.3) 1.10 (0.80, 1.52) 1.18 (0.84, 1.66)

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Table 3. The Effect of Smoking Status on the Association between IL-10 Genetic Variants and the Risk of Gastric Cancer, Stratified

by Histological Type

aUpper numbers are numbers of controls/cases, and lower numbers are adjusted odds ratios and 95% confidence intervals in parenthesis. Adjustment was done for age, sex, and H.

pylori infection.

All Intestinal type Diffuse type

Non-smoker Past smokerCurrent

smokerNon-smoker Past smoker Current smoker Non-smoker Past smoker

Current

smokerRegardless of genetic variants

208/138 158/108 129/204 208/64 158/71 129/118 208/108 158/29 129/77

1.0 (ref) 0.98 (0.63, 1.51) 2.19 (1.44, 3.33) 1.0 (ref) 1.46 (0.84, 2.52) 3.56 (1.92, 5.54) 1.0 (ref) 0.57 (0.32, 1.03) 1.59 (0.95, 2.65)

IL-10-1082

AA 180/155 140/191 115/170 180/55 140/59 115/95 180/91 140/24 115/67

1.0 (ref) 0.95 (0.60, 1.49) 2.02 (1.30, 3.11) 1.0 (ref) 1.38 (0.78, 2.44) 2.87 (1.66, 4.97) 1.0 (ref) 0.53 (0.29, 0.99) 1.52 (0.89, 2.58)

G carrier 28/28 18/17 14/34 28/9 18/12 14/23 28/17 18/5 14/10

1.08 (0.60, 1.96) 1.18 (0.55, 2.57) 3.80 (1.80, 8.01) 1.07 (0.46, 2.50) 1.94 (0.79, 4.73) 6.82(2.94, 15.84) 0.94 (0.47, 1.88) 0.79 (0.26, 2.41) 2.14 (0.82, 5.60)

IL-10-592

AA 105/90 72/46 71/95 105/26 72/26 71/55 105/55 72/13 71/34

1.0 (ref) 0.89 (0.51, 1.57) 1.92 (1.13, 3.25) 1.0 (ref) 1.36 (0.65, 2.86) 3.28 (1.64, 6.54) 1.0 (ref) 0.50 (0.23, 1.10) 1.29 (0.67, 2.48)

C carrier 103/93 86/62 58/109 103/38 86/45 58/63 103/53 86/16 58/43

1.06 (0.70, 1.61) 1.09 (0.64, 1.87) 2.63 (1.56, 4.45) 1.49 (0.82, 2.69) 2.16 (1.09, 4.30) 4.91 (2.49, 9.69) 1.02 (0.63, 1.67) 0.63 (0.30, 1.32) 1.95 (1.04, 3.66)

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Figure 1. Combined Effects of Smoking (S) and H. pylori (Hp) Infection on the Association between IL-10 Genetic

Variants and Noncardia Gastric Cancer, Stratified by Histological Types

Gastric cancer and salt preference: a population-based

cohort study in Korea1–3

Jeongseon Kim, Sohee Park, and Byung-Ho Nam

1 From the Cancer Epidemiology Branch (JK) and the Cancer Biostatistics Branch (SP and B-HN),

Division of Cancer Epidemiology and Management, National Cancer Center Research Institute, Goyang-si,

Gyeonggi-do, South Korea.2 Supported by The National Cancer Center, Korea (grant 0810190).3 Address correspondence to B-H Nam, Cancer Biostatistics Branch, Division of Cancer Epidemiology

and Management, National Cancer Center Research Institute, 111 Junbalsan-ro, Ilsandong-gu, Goyang-si,

Gyeonggido, 410-769, South Korea. E-mail: byunghonam@ncc.re.kr.

Am J Clin Nutr 2010;91:1289–93.

Abstract

Background: Although the incidence of gastric cancer is declining, it remains the most common cancer in

Korea. There have been discrepancies in epidemiologic studies regarding a causal relation between highly salted

food and the risk of gastric cancer.

Objective: The aim of this study was to assess the effect of salt preference on the incidence of gastric cancer

in Korean adults through a population-based, prospective cohort study.

Design: Participants were Korean government employees, school faculty members, and their unemployed

dependents, aged 30–80 y, who underwent health examinations between 1996 and 1997. In 2003, information

on the gastric cancer incidence in these participants was obtained during the 6–7-y follow-up period. The final

data analysis included 2,248,129 study subjects. The hazard ratio (HR) and 95% CI of the HR were estimated by

using the Cox proportional hazards regression model.

Results: The age-standardized incidence rates per 100,000 person years for the overall total population, men

only, and women only were 97.64, 136.03, and 52.90, respectively. The Cox proportional hazards regression

model, with adjustment for possible confounding factors, showed evidence of an increased risk of gastric cancer

with salt preference. The HRs were 1.10 (95% CI: 1.04, 1.16) and 1.10 (95% CI: 1.03, 1.17) for the overall total

population and men only, respectively.

Conclusion: The current findings suggest that salt preference has a marginal positive association with a risk

of gastric cancer. Am J Clin Nutr 2010;91:1289–93.

Fresh and pickled vegetable consumption and

gastric cancer in Japanese and Korean populations:

A meta-analysis of observational studies

Hyun Ja Kim1, Sun Young Lim2, Jung-Sug Lee2, Sohee Park3,

Aesun Shin2, Bo Youl Choi1, Taichi Shimazu4,5, Manami Inoue4,5,

Shoichiro Tsugane4,5, Jeongseon Kim2

1Department of Preventive Medicine, Hanyang University College of Medicine, Seoul, Korea2Cancer Epidemiology Branch, Research Institute, National Cancer Center, Goyang, Korea3Cancer Registration & Statistics Branch, National Cancer Control Research Institute, National Cancer

Center, Goyang, Korea4Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National

Cancer Center, Tokyo, Japan5 Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan

Cancer Sci 2010; 101: 508–516

327

253.9

189

0

50

100

150

200

250

300

350m

ean

dail

y v

eg

etab

le i

ntake

(g

/day)

Korea Japan USA

Incidence rate per 100,000

69.7

62.0

41.4

36.7

22.3

18.8

15.1

15.7

12.5

12.4

10.8

9.6

10.4

9.1

7.2

4.8

26.8

26.1

19.2

15.8

11.1

9.7

8.8

7.2

5.5

5.2

4.6

6.0

4.1

4.0

3.3

3.0

0 10 20 30 40 50 60 70 80 90 100

한국

일본

중국

러시아

싱가폴

이탈리아

독일

스페인

영국

네덜란드

스위스

핀란드

프랑스

캐나다

미국

쿠웨이트

MenWomen

IARC, GLOBOCAN 2008, http://www-dep.iarc.fr/

Age was adjusted to World Standard Population. .

Age-standardized incidence rates for stomach among some selected population, 2008

• To examine the relationships between the

consumption of fresh vegetables and pickled

vegetables and GC risk through a meta-analysis

of studies conducted in Japanese and Korean

populations that demonstrated a high-risk of GC

but also a high intake of vegetables.

Meta-analysis

Definition: A method used to combine

the results of several studies

addressing similar questions

Figure 1. Summary estimate of the relationships between fresh vegetable intake and gastric cancer risk in

Japanese and Korean populations. CI, confidence interval; OR, odds ratio; RR, relative risk. Shaded box,

point estimate of each study; horizontal line, 95% CI of each study; diamond, summary point estimate and

its 95% CI of studies.

Figure 2. Summary estimate of the relationships between pickled vegetable intake and gastric cancer risk

in Japanese and Korean populations. CI, confidence interval; OR, odds ratio; RR, relative risk. Shaded

box, point estimate of each study; horizontal line, 95% CI of each study; diamond, summary point

estimate and its 95% CI of studies.

• The anticarcinogenic effect of vegetables is attributed in

part to the effect of antioxidant vitamins, especially vitamin

C and β-carotene, which inhibit the intragastric formation

of carcinogens such as N-nitroso compounds from

secondary amines and nitrite.

• Another possible mechanism for the anticarcinogenic

effects of antioxidants is the neutralization of reactive

oxygen free radicals that can damage DNA.

• Pickled vegetables contain a substantial amount of salt.

Salt is not a directly acting carcinogen, but consumption of

salt and salt-preserved foods may cause atrophic gastritis

by directly damaging the gastric mucosa, which could

induce DNA synthesis and cell proliferation that

contributes to stomach carcinogenesis or enhance the

penetration of carcinogens.

• A high-salt diet enhances H. pylori colonization in the

stomach. H. pylori infection may increase the endogenous

synthesis of nitrate in the stomach and decrease gastric

vitamin C concentrations, thereby increasing endogenous

N-nitroso compound formation.

• The results of this meta-analysis provide evidence

that high intake of pickled vegetables was associated

with an increased GC risk, whereas high intake of

fresh vegetables was associated with a decreased GC

risk.

• These results may explain why the GC incidence rates

in Japan and Korea remain high despite a high

consumption of vegetables in these countries.

• A high consumption of fresh vegetables, rather than

the total amount of vegetables, which includes

pickled vegetables, should be promoted to reduce

GC rates in Japan and Korea.

Thank You for Your Attention!