Risk Of Noncardia Gastric Cancer Research Articles

Effects of Polymorphisms of Innate Immunity Genes and Environmental Factors on the Risk of Noncardia Gastric Cancer

PurposeIncreasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori-induced inflammation and may influence susceptibility in developing noncardia gastric cancer. Therefore, we investigate the effect of polymorphisms of innate immunity genes and interactions with environmental factors in the Korean population.Materials and MethodsWe genotyped four polymorphisms of TLR2 (rs1898830), TLR4 (rs10983755 and rs10759932), and CD14 (rs2569190) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Polytomous logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which were stratified by the histological type of gastric cancer.ResultsTLR4 rs10983755 A carriers were found to have higher risk of intestinal-type noncarida gastric cancer than G homozygotes (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.01 to 1.97), but other genetic variants showed no association with the risk of noncardia gastric cancer. Among H. pylori-positive participants, smokers carrying TLR4 rs10983755 A had a higher risk of intestinal-type gastric cancer than nonsmoking TLR4 rs10983755 G homozygotes (OR, 4.28; 95% CI, 2.12 to 8.64). In addition, compared with tap water, other drinking water sources during childhood were found to be associated with the elevated risk of intestinal-type gastric cancer, and these associations were slightly stronger among TLR4 rs10983755 A carriers.ConclusionThe genetic polymorphisms of innate immunity genes are associated with the development of intestinal-type noncardia gastric cancer and these associations may differ in accordance to an exposure to certain environmental factors.

Analysis of the association of interleukin-17 gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population

We aimed to explore the association between interleukin-17 (IL-17) polymorphisms, Helicobacter pylori infection, and subsites in gastric cancer risk in a Chinese population. We genotyped three promoter polymorphisms (rs2275913G>A, rs3748067C>T, and rs763780T>C) of IL-17 in a case-control study of 260 gastric cancer patients and 512 healthy controls. An unconditional multiple logistical regression model was used to calculate the effects of IL-17 gene polymorphisms on gastric cancer risk. The rs2275913 AA (adjusted OR = 1.69, 95 % CI = 1.15-2.49) and rs3748067 TT (adjusted OR = 1.73, 95 % CI = 1.03-2.94) genotypes were associated with an increased risk of gastric cancer. We observed a significant interaction among rs2275913G>A, rs3748067C>T, and H. pylori infection on the risk of gastric cancer (p for interaction of 0.036 and 0.048, respectively). H. pylori infection subjects carrying the rs2275913 AA (adjusted OR = 2.48, 95 % CI = 1.49-4.12) and rs3748067 TT (adjusted OR = 2.54, 95 % CI = 1.34-5.12) genotypes had a greatly increased risk of gastric cancer compared to negative H. pylori participants. Similarly, subjects carrying the rs2275913 AA (adjusted OR = 2.09, 95 % CI = 1.25-3.45) and rs3748067 TT (adjusted OR = 2.29, 95 % CI = 1.20-4.20) genotypes had a moderately increased risk of noncardia gastric cancer. A significant interaction was observed between the rs2275913G>A and rs3748067C>T genotype and subsites of gastric cancer (p for interaction of 0.044 and 0.008, respectively). The rs2275913G>A and rs763780T>C polymorphisms increase gastric cancer risk, and interact with H. pylori infection and subsites. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer.

Body mass index and socioeconomic status measured in adolescence, country of origin, and the incidence of gastroesophageal adenocarcinoma in a cohort of 1 million men

To the authors' knowledge, little work has been done concerning adolescent precursors for gastroesophageal cancer. In the current study, the association of adolescent overweight as well as socioeconomic status (SES) with the incidence of esophageal adenocarcinoma (EAC), gastroesophageal junction adenocarcinoma (GEJAC), and noncardia gastric cancer (NCGC) was evaluated. Body mass index (BMI) was measured in 1 million Israeli adolescent males who underwent a general health examination at a mean age of 17.3 ± 0.5 years from 1967 to 2005. Overweight was defined as a BMI ≥ 85th percentile of the standard US distribution in adolescence. Incident cancer was identified by linkage with the Israeli National Cancer Registry. A total of 182 incident cancer cases were documented (52 combined EAC and GEJAC cases and 130 NCGC cases). Adolescent overweight at baseline (BMI ≥ 85th percentile) was associated with an increased risk in the combined group of cases of EAC and GEJAC (multivariable hazards ratio [HR], 2.1; 95% confidence interval [95% CI], 1.1-4.3 [P = .032]). Low SES (the lowest category vs the highest) as well as low number of years of education (≤ 9 years) were associated with an increased risk of intestinal-type NCGC (multivariable HR, 2.2; 95% CI, 1.0-4.8 [P = .041] and multivariable HR, 1.9; 95% CI, 1.1-3.19 [P = .020], respectively). The adjusted risk of NCGC was higher in immigrants born in Asian countries and the former Soviet Union. Overweight during adolescence was found to be substantially associated with the subsequent development of EAC and GEJAC. In addition, although potential confounding by Helicobacter pylori infection status or lifestyle factors was not fully accounted for in the analyses, lower SES as well as immigration from higher-risk countries are important determinants of NCGC.

Variants of Interleukin-16 Associated with Gastric Cancer Risk

We conducted a case-control matched study to investigate the role of IL-16 gene polymorphisms, rs4072111, rs1131445, rs4778889 and rs11556218, in the risk of gastric cancer in a Chinese population, also performing subgroup analysis by subsites. To test the hypothesis of involvement, we analyzed the four SNPs of IL16 in 347 cancer patients and 368 controls. Demographic data and other information were collected using a newly designed questionnaire. Genotyping of IL16 (rs4072111, rs1131445, rs4778889 and rs11556218) was performed in a 384-well plate format on the MassARRAY® platform. In our study, we found the gastric cancer patients were more likely to be male and have a family history of cancer (P < 0.05). We found the rs4778889 CC and rs11556218 GG genotype was significantly associated with 1.97 and 1.84-fold increased risk of non-cardia gastric cancer, while we did not find significant association between the four IL-16 SNPs and cardia gastric cancer. In conclusion, our study indicated that IL-16 rs4778889 CC and rs11556218 GG genotypes are associated with an increased risk of non-cardia gastric cancer in a Chinese population. Our results offer insights into the influence of IL-16 on development of gastric cancer.

Cruciferous vegetable consumption and gastric cancer risk: A meta‐analysis of epidemiological studies

The relationship between consumption of cruciferous vegetables (CV) and risk of gastric cancer has been investigated by many studies, but remains controversial. We carried out a meta-analysis to summarize available evidence from epidemiological studies on this point. Relevant published reports of CV intake and gastric cancer were identified using MEDLINE (PubMed), EMBASE, and Web of Science databases through to the end of September 2012. We pooled the relative risk from individual studies using a fixed- or random-effects model and carried out heterogeneity and publication bias analyses. Sixteen case-control and six prospective studies were included in our analysis. When all studies were pooled, we yielded a significantly inverse association between CV (relative risk = 0.81; 95% confidence interval, 0.75-0.88) intake and gastric cancer risk, with little heterogeneity (Q = 27.27, P = 0.292, I(2) = 12.0%). Specific analysis for cabbage intake yielded similar result. When separately analyzed, case-control studies of CV intake yielded significant results and the results of prospective studies showed borderline statistical significance. Moreover, significant results were consistent for high-quality studies, for North American, European, and Asian studies, for studies on males, and for studies on non-cardia gastric cancer. Findings from this meta-analysis provide evidence that high intake of CV was inversely associated with the risk of gastric cancer and non-cardia gastric cancer in humans. Further studies on other specific CV, food preparation methods, and stratified results by anatomic cancer site and histological type should be extended in the future.

Interleukin-10 Gene Promoter Polymorphisms and Risk of Gastric Cancer in a Chinese Population: Single Nucleotide and Haplotype Analyses

Interleukin (IL) -10 is a potent cytokine with a dual ability to immunosuppress or immunostimulate. We aimed to explore the association of IL10 promoter polymorphisms with risk of gastric cancer (GC) in a Han population in Southwestern China. We enrolled 308 pairs of GC and control subjects from four hospitals and a community between October 2010 and August 2011 in a 1:1 matched case-control design. Demographic information was collected using a designed questionnaire. IL10-592 A>C and IL10-1082 A>G polymorphisms were determined by Sequenom MassARRAY analysis. Patients with GC reported statistically higher proportions of family history of cancer (29.9% versus 10.7%, P<0.01) and alcohol drinking (54.6% versus 43.2%, P<0.01) than did controls. Similar results were observed in comparison between non-cardia GC patients and controls (P<0.01 and P=0.03). Variant genotypes of IL10-592 A>C and IL10-1082 A>G were not associated with overall GC risk (adjusted OR, 0.94, 95% CI, 0.66-1.33; adjusted OR, 1.00, 95% CI, 0.62-1.60). Sub-analysis showed that the IL10-592 AC/CC variant genotype was associated with decreased non-cardia GC risk (adjusted OR, 0.58; 95% CI, 0.36-0.95). No association was found between any of the IL10 haplotypes established from two polymorphisms and risk of non-cardia GC. In conclusion, our data do not link the two SNPs of IL10-592 and IL10-1082 with overall GC risk. We demonstrate that IL10-592 polymorphism is associated with protective effect against non-cardia GC. Our findings may offer insight into risk associated with the development of GC in this region.

Abstract 2543: A genome-wide analysis of ROHs identifies two susceptibility regions for non-cardia gastric cancer in han Chinese.

Abstract Runs of homozygosity (ROHs) are a novel class of genomic variation and may involve in the individual susceptibility to diseases. To better understand ROH and its relationship with non-cardia gastric cancer, we performed a genome-wide ROH analysis in two independent case-control studies (Nanjing study: 565 cases and 1,162 controls; and Beijing study: 468 cases and 1,123 controls) from Han Chinese populations. ROHs with a length from 0.5 to 1.5 Mb defined by at least 50 single nucleotide polymorphisms (SNPs) were evaluated with the association of non-cardia gastric cancer risk using genome-wide SNP data. We found that the overall ROH levels were significantly associated with a decreased risk of non-cardia gastric cancer risk (odds ratio (OR) =0.60; 95% confidence interval (CI): 0.50-0.73; P = 2.95×10-7). We also identified two ROHs at 15q13.2 and 2q14.2 that were consistently associated with non-cardia gastric cancer risk in both the Nanjing study (15q13.2: OR=0.55; and 2q14.2: OR=1.69) and the Beijing study (15q13.2: OR=0.41; and 2q14.2: OR=1.67). After combining the two studies, the association reached genome-wide significance level (9,749 ROHs, P&amp;lt;5×10-6) for 15q13.2 (OR=0.51, 95%CI: 0.38-0.67, P=2.49×10-6) but not 2q14.2 (OR=1.68, 95%CI: 1.30-2.18, P=9.06×10-5). These results suggest that overall ROH levels may play a protective effect against non-cardia gastric cancer, and 15q13.2 and 2q14.2 regions may be new susceptibility loci for non-cardia gastric cancer. Citation Format: Zhibin Hu, Cheng Wang, Guangfu Jin, Dongxin Lin, Hongbing Shen. A genome-wide analysis of ROHs identifies two susceptibility regions for non-cardia gastric cancer in han Chinese. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2543. doi:10.1158/1538-7445.AM2013-2543

A missense SNP in the codon of ADD1 phosphorylation site associated with non-cardia gastric cancer susceptibility in a Chinese population

This study investigated the association between a missense SNP in the codon of ADD1 phosphorylation site and the susceptibility of non-cardia gastric cancer in a Chinese population. PhosphoSitePlus and dbSNP database were combined to discover missense SNPs in the codon of phosphorylation site. Then, we genotyped the missense SNP in 1, 998 cases with non-cardia gastric cancer and 2, 008 cancer-free controls of Chinese descent. Analysis was conducted by using Logistic model adjusted by gender and age. The rs4963 in the codon of ADD1 phosphorylation site was found. The frequencies of the 3 rs4963 genotypes, CC, CG, GG, among controls were 25.2%, 50.4%, and 24.4%, respectively, among patients were 20.1%, 50.6%, and 29.3%, respectively. Compared with CC genotype, the rs4963 CG genotype and GG genotype significantly increased the risk of non-cardia gastric cancer with the odds ratios being 1.24 (95%CI: 1.06 ∼ 1.46, P = 0.008) and 1.49 (95%CI: 1.25 ∼ 1.78, P < 0.001), respectively. Fnnctional polymorphism in the phosphorylation site of ADD1 (rs4963) may influence the susceptibility of non-cardia gastric cancer.

Polymorphisms of XRCC1 and ADPRT Genes and Risk of Noncardia Gastric Cancer in a Chinese Population: a Case-control Study

Gastric cancer (GC) is one of the most common malignancies and its mortality ranks third among all cancers in China. We previously noted that XRCC1 Arg194Trp was associated with GC risk in Western China in a study on XRCC1 Arg194Trp and ADPRT Val762Ala. We aimed to further explore the association of these polymorphisms with risk of the noncardia subtype. We enrolled 176 noncardia GC patients and 308 controls from four hospitals and a community between October 2010 and August 2011. Genotyping was performed in a 384-well plate format on the Sequenom MassARRAY platform. A self-designed questionnaire was utilized to collect epidemiological data from the subjects regarding demographic factors and potential risk factors. Subjects were aged 56.8±11.8 (mean±standard deviation) and 57.6±11.1 years in the case and control groups, respectively. Individuals carrying the XRCC1 Trp/Trp or Arg/Trp variant genotype were at significantly increased risk of noncardia GC (adjusted OR, 1.48; 95% CI, 1.00-2.17), after adjustment for family history of cancer, drinking, and smoking. The increased risk of XRCC1 Arg194Trp variant genotype was more pronounced among subjects below 60 years old (adjusted OR, 1.78; 95% CI, 1.07-2.96), compared to older individuals. ADPRT Val762Ala variants (Ala/Ala or Val/Ala) were not associated with noncardia GC (adjusted OR, 1.03; 95% CI, 0.69-1.54). Our study suggests that XRCC1 Arg194Trp is a genetic susceptibility factor for developing noncardia GC in Han Chinese in Western China. In particular, individuals with the XRCC1 Arg194Trp variant genotype are at increased risk for GC below 60 years old.

Impact of methylenetetrahydrofolate reductase C677T polymorphism on the risk of gastric cancer and its interaction with Helicobacter pylori infection.

Attempts for early detection of gastric cancer have recently focused on host's genetic susceptibility factors and gene-environment interactions. We have, herein, studied the association of MTHFR C677T single nucleotide polymorphism (SNP) and its interaction with Helicobacter pylori infection, smoking, age and gender on the risk of gastric cancer among an Iranian population. Gastric cancer patients (n = 450) and cancer-free controls (n = 780) were studied for serum H. pylori-specific IgG antibodies by ELISA and MTHFR C677T polymorphism (SNP) by PCR-RFLP. Demographic and life style data were collected through patient interviews. Unconditional logistic regression model estimated odds ratio (OR) and the corresponding 95% confidence intervals (CI). The interactions of MTHFR genotype with H. pylori infection (P = 0.03), age (P = 0.049) and gender (P = 0.007) were statistically significant. Accordingly, MTHFR C677T carriers who were also positive for H. pylori infection exhibited 80% (OR = 1.8, 95% CI = 1.0-2.9) significant excess risk of non-cardia gastric cancer. Furthermore, subjects over the age of 50 or female subjects carrying MTHFR C677T SNP showed 40 (OR = 1.4, 95% CI = 1.0-2.0) and 100 (OR = 2.0, 95% CI = 1.2-3.2) percent increased risk of gastric cancer, respectively. MTHFR C677T SNP seems to increase the risk of gastric cancer and the effect is significantly inflated by interactions with H. pylori infection, age and gender.

Interaction between Dietary Factors and Helicobacter Pylori Infection in Noncardia Gastric Cancer: A Population-Based Case-Control Study in China

Background: The aim of this study was to investigate the relationships among Helicobacter pylori, dietary factors, and the risk of noncardia gastric cancer in a hospital-based case-control study in China.Methods: A case-control study of noncardia gastric cancer was performed at 3 hospitals in Xi'an, China, between September 2008 and July 2010. Participants were 257 men and women with histologically diagnosed primary noncardia gastric cancer and 514 sex- and age-matched (± 5 years) control subjects selected from the communities where the cases were living when diagnosed. A questionnaire was used to obtain information regarding potential risk factors, including diet, and blood samples were obtained to examine H pylori infection status.Results: Positive H pylori status (odds ratio [OR], 3.2; 95% confidence interval [CI], 0.8–5.9) and high consumption of pickled foods (OR, 27.1; 95%, 8.7–79.1) appeared to increase the risk of noncardia gastric cancer, whereas high consumption of vegetables (OR, 0.3; 95% CI, 0.1–0.89), fruits (OR, 0.2; 95% CI, 0.09–0.81), and soya products (OR, 0.04; 95% CI, 0.01–0.3) appeared to decrease the risk. Consumption of meat, cereals, tubers, eggs, oils, nuts, fish, fresh fruit, and red meat was not clearly associated with risk. Effect modification was observed, such that a relatively high consumption of fruit and vegetables appeared to attenuate the association of H pylori with risk of noncardia gastric cancer (p < 0.05).Conclusions: Our data suggest that noncardia gastric cancer is highly preventable through modifications in dietary habits. Given the prevalence of H pylori infection worldwide, information regarding potential interaction between H pylori and lifestyle factors in gastric cancer development, including the dietary factors examined in our study, may prove valuable in future efforts at prevention.

Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project

In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®)). By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

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

ObjectiveBoth variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans.MethodsWe genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer.ResultsThe IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI] = 17.76 [6.17−51.06]) or the -592C (OR [95% CI] = 8.37 [2.79−25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction = 0.080).ConclusionsInflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer.

Abstract A64: Effects of genetic polymorphisms of innate immunity genes on the noncardia gastric cancer risk

Abstract Background and Objective: Increasing evidence suggests that polymorphisms in innate immunity genes are associated with Helicobacter pylori (H. pylori)-induced inflammation and may influence susceptibility to developing noncardia gastric cancer. Therefore, we investigated the effect of polymorphisms of TLR2, TLR4, and CD14, their combination and interaction with environmental factors on the noncardia gastric cancer risk in a Korean population. Methods: We genotyped four polymorphisms in three genes (TLR2, rs1898830 A&amp;gt;G; TLR4, rs10759932 T&amp;gt;C, rs10983755 A&amp;gt;G; CD14, rs2569190 T&amp;gt;C) in a case-control study of 487 noncardia gastric cancer patients and 487 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of genetic polymorphisms and environmental factors, which was stratified by the histological type of gastric cancer. Results: TLR4 rs10983755 variant allele carriers were found to have a higher risk of intestinal type gastric cancer than homozygous wild-type carriers (OR [95% CI] = 1.40 [1.01–1.96], P = 0.046). Other genetic variants did not show any association with noncardia gastric cancer risk. When we examined the combined effect with other polymorphisms, the increased risk of intestinal type gastric cancer among TLR4 rs10983755 variant allele carriers compared to wild-type homozygous carriers were observed only among homozygous wild-type carriers of TLR2 rs1898830 (OR [95% CI] = 1.97 [1.24–3.12], P = 0.004) or CD14 rs2569190 (OR [95% CI] = 1.95 [1.31–2.91], P = 0.001). In addition, the effect of TLR4 rs10983755 variant allele on intestinal type gastric cancer was stronger among H. pylori-positive participants who are under 55 years old, smoke tobacco and drink alcoholic beverages. Conclusion: These results suggest that the genetic polymorphisms of these innate immunity genes are associated with the development of H. pylori-associated noncardia gastric cancer. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A64.

Alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Gastric cancer (GC) is the second leading cause of cancer death worldwide. The association between alcohol consumption and GC has been investigated in numerous epidemiologic studies with inconsistent results. We evaluated the association between alcohol consumption and GC risk. We conducted a prospective analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 444 cases of first primary gastric adenocarcinoma. HRs and 95% CIs for GC were estimated by using multivariable Cox proportional hazards regression for consumption of pure ethanol in grams per day, with stratification by smoking status, anatomic subsite (cardia, noncardia), and histologic subtype (diffuse, intestinal). In a subset of participants, results were further adjusted for baseline Helicobacter pylori serostatus. Heavy (compared with very light) alcohol consumption (≥60 compared with 0.1-4.9 g/d) at baseline was positively associated with GC risk (HR: 1.65; 95% CI: 1.06, 2.58), whereas lower consumption amounts (<60 g/d) were not. When we analyzed GC risk by type of alcoholic beverage, there was a positive association for beer (≥30 g/d; HR: 1.75; 95% CI: 1.13, 2.73) but not for wine or liquor. Associations were primarily observed at the highest amounts of drinking in men and limited to noncardia subsite and intestinal histology; no statistically significant linear dose-response trends with GC risk were observed. Heavy (but not light or moderate) consumption of alcohol at baseline (mainly from beer) is associated with intestinal-type noncardia GC risk in men from the EPIC cohort.

Abstract 3745: IL-10 polymorphisms, smoking, and Helicobacter pylori infection on the risk of noncardia gastric cancer in Koreans

Abstract Background: Genetic variations of interleukin-10 (IL-10) and environmental factors are assumed to influence inflammation and gastric carcinogenesis. Therefore, we aimed to investigate the association between IL-10 polymorphisms, smoking, and Helicobacter pylori (H. pylori) infection on the noncardia gastric carcinogenesis in Koreans. Methods: We genotyped 3 promoter polymorphisms (−1082 A&amp;gt;G, -819T&amp;gt;C, -592A&amp;gt;C) on the IL-10 gene in 495 noncardia gastric cancer patients and 495 sex- and age-matched controls. Multiple logistic regression models were used to detect the effects of IL-10 genetic variants, smoking, and H. pylori infection on gastric cancer risk, stratified by histological type of gastric cancer. Results: The IL-10-819C allele and -592C allele are in complete linkage disequilibrium, and IL-10-819C/-592C carriers are associated with a higher risk of noncardia gastric cancer, particularly with a risk of intestinal type cancer (OR [95% CI] = 1.50 [1.08−2.08]), than those with the wild type homozygote genotypes. Compared to nonsmokers carrying the wild type homozygotes, current smokers carrying IL-10-1082G and -819C/-592C showed 4.91 (95% CI = 2.49−9.69) and 6.82 (95% CI = 2.94−15.84) times increased risk of intestinal type gastric cancer, respectively. In addition, smokers with H. pylori infection were in the highest risk of intestinal gastric cancer compared with non-smokers without H. pylori infection, and this association was particularly stronger among IL-10-1082G carriers than AA carriers (OR [95% CI] = 15.54 [5.52−43.72]). Conclusion: Inflammation-related genetic variants may interact with smoking and H. pylori infection on the risk of noncardia gastric cancer, particularly intestinal type. Therefore, high risk group may reduce the risk of gastric cancer by modifying their lifestyles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3745. doi:10.1158/1538-7445.AM2011-3745

Genetic Variation in the Prostate Stem Cell Antigen Gene and Upper Gastrointestinal Cancer in White Individuals

An association between gastric cancer and the rs2294008 (C>T) polymorphism in the prostate stem cell antigen (PSCA) gene has been reported for several Asian populations. We set out to determine whether such an association exists in white individuals. We genotyped 166 relatives of gastric cancer patients, including 43 Helicobacter pylori-infected subjects with hypochlorhydria and gastric atrophy, 65 infected subjects without these abnormalities, 58 H pylori-negative relatives, and 100 population controls. Additionally, a population-based study of chronic atrophic gastritis provided 533 cases and 1054 controls. We then genotyped 2 population-based, case-control studies of upper gastrointestinal cancer: the first included 312 gastric cancer cases and 383 controls; the second included 309 gastric cancer cases, 159 esophageal cancer cases, and 211 controls. Odds ratios were computed from logistic models and adjusted for confounding variables. Carriage of the risk allele (T) of rs2294008 in PSCA was associated with chronic atrophic gastritis (adjusted odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.1-1.9) and noncardia gastric cancer (OR, 1.9; 95% CI: 1.3-2.8). The association was strongest for the diffuse histologic type (OR, 3.2; 95% CI: 1.2-10.7). An inverse association was observed between carriage of the risk allele and gastric cardia cancer (OR, 0.5; 95% CI: 0.3-0.9), esophageal adenocarcinoma (OR, 0.5; 95% CI: 0.3-0.9), and esophageal squamous cell carcinoma (OR, 0.4; 95% CI: 0.2-0.9). The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers.

Individual and combined effects of foods on helicobacter pylori growth

Eradication of H. pylori can reduce the risk of non-cardia gastric cancer developing in infected humans. Thus, the consumption of foods that inhibit the growth of these bacteria may provide an alternative to current therapies that include antibiotics, proton pump inhibitors and/or bismuth salts. This study describes a simple broth dilution assay developed to screen a range of foods for their individual and combined effects on H. pylori growth. It was found that foods with measurable anti-H. pylori activity have an effect greater in combination than the sum of foods tested singly, and that this was most noticeable with a combination of broccoli sprouts and blackcurrant oil. The results suggest that food synergy should be considered in any nutraceutical approach to H. pylori infection.

T2009 Assessment of Novel Genetic Polymorphisms and Risk of Upper Gastrointestinal Carcinoma

Introduction Upper gastrointestinal malignancies comprising gastric and oesophageal cancers remain a major global health problem. Recently, genome wide association studies have been used to identify risk factors for several diseases. Four SNPs identified at chromosome regions 8q24 and 9p24 (rs6983267, rs10505477, rs1447295 and rs719725) have been shown to increase risk of various solid tumours including prostate and colorectal cancer, but have not been studied in the context of upper GI cancer. Methods Two case-control studies were used to assess SNP frequency: Study 1- a gastric cancer case-control study derived from a Caucasian population in Warsaw, Poland with DNA available from 312 non-cardia gastric adenocarcinoma patients and 419 controls, Study 2- a multicentre oesophageal and gastric cancer study from the US with DNA available from 307 subjects with gastric adenocarcinoma, 159 subjects with oesophageal cancer and 211 population controls. DNA was genotyped by 5′ nuclease PCR assay. Hardy-Weinberg equilibrium of alleles at individual loci was assessed using χ 2 test. OR with Cornfield 95% CIs were computed by logistic regression using Stata V.7.0 software. Results Genotyping and statistical analysis of the 4 SNPs was completed on 765 cases and 583 controls. Individuals carrying the C/C genotype of rs1447295 had an elevated risk for non-cardia gastric cancer (OR 1.57, 95% CI 1.03 to 2.45). Individuals carrying the A/A genotype of rs1447295 had an increased risk of squamous cell oesophageal cancer (OR 7.4, 95% CI 1.4 to 49). None of the other three SNPs tested in this study showed any statistically significant associations. Conclusion The association between the rs1447295 SNP and risks of gastric and oesophageal cancer are novel and offer an opportunity to explore the genetic basis of these malignancies. Our study has extended the genetic link between the 8q24 region and risk of yet another group of solid tumours. Extensive efforts should focus on evaluating the functional significance of this region in the context of the molecular pathogenesis of these malignancies.

LTA 252GG and GA Genotypes are Associated with Diffuse‐Type Noncardia Gastric Cancer Risk in the Japanese Population

There are limited numbers of reports on the association of lymphotoxin-alpha (LTA) genotypes with gastric cancer. A nested case-control study was carried out in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years) and blood cells. Enrolled were 287 cases with noncardia gastric cancer of diffuse and intestinal types and three controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and counter-matched on radiation dose. LTA 252GG and GA genotypes were associated with the prevalence of Helicobacter pylori IgG seropositivity and higher antibody titer against H. pylori cytotoxin-associated gene A (CagA) protein in controls and they were an independent risk factor for noncardia gastric cancer of diffuse type (RR = 2.8 (95% CI: 1.3-6.3), p = .01, and RR = 2.7 (95% CI: 1.5-4.8), p < .001), but not for intestinal type, after adjusting for H. pylori IgG seropositivity, CagA antibody titers, chronic atrophic gastritis, smoking, and radiation dose. Cessation of smoking (RR = 0.4 (95% CI: 0.2-0.7), p < .001) and never smoking (RR = 0.4 (95% CI: 0.3-0.6), p < .001) were both protective for future noncardia gastric cancer. Radiation dose was associated with noncardia gastric cancer in subjects with both the LTA 252G-allele and never smoking/quit smoking histories (RR = 3.8 (95% CI: 1.7-5.9), p = .009). The LTA 252 genotype is associated with noncardia gastric cancer of diffuse type in Japan and interacted with radiation dose.