Risk Of Intestinal Gastric Cancer Research Articles

Interaction of H. pylori with toll-like receptor 2-196 to -174 ins/del polymorphism is associated with gastric cancer susceptibility in southern China.

Genetic polymorphisms of Toll-like receptors play important roles in gastric carcinogenesis. The aim of this study was to determine the role of TLR2-196 to -174 ins/del polymorphism in gastric cancer susceptibility and prognosis. This study included 520 people from southern China. Samples were genotyped by the allele-specific polymerase chain reaction, among which 10% were randomly selected for sequencing. The serological method was used to determine Helicobacter pylori. The TLR2 genotype was not associated with the risk of H. pylori infection. The del/del genotype exhibited significantly higher gastric cancer risk (adjusted OR 2.59, 95% CI 1.33‒5.07) than that of the ins/ins genotype. Further stratification analyses demonstrated that the del/del genotype was associated with a risk of intestinal gastric cancer (adjusted OR 2.62, 95% CI 1.34-5.14). In addition, the presence of the del/del genotype and the H. pylori infection conferred a synergistic effect (OR 3.04, 95% CI 1.33‒6.98) for the development of gastric cancer. The del/del genotype was not associated with a poor prognosis in gastric cancer patients. The del/del genotype is associated with an increased gastric cancer risk in the southern Chinese population. However, TLR2 polymorphism is neither associated with H. pylori infection, nor with a poor prognosis.

TGF-α gene variations and increased susceptibility of gastric cancer in an eastern Chinese Han population

Transforming growth factor-alpha (TGF-α) correlates with deep invasion, advanced stage and poor prognosis in gastric cancer. Genetic variants in the 3′ untranslated region (UTR) of TGF-α gene may influence the stability and post-transcriptional regulation of mRNA and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped five polymorphisms in 3′UTR (rs3771527, rs503314, rs473698, rs3732253 and rs538118) and one in 3′ near region (rs11466306) of the TGF-α gene by polymerase chain reaction-ligation detection reaction methods (PCR-LDR). We found that GA/AA genotype of rs11466306 in the 3′ near gene could increase the risk of overall gastric cancer (adjusted OR = 1.499, 95%CI: 1.101–2.041), compared to the wild homozygous GG genotype. Meanwhile, the risk effect was more obvious in the intestinal gastric cancer and gastric noncardia cancer (adjusted OR = 1.682, 95%CI: 1.188–2.380; adjusted OR = 1.495, 95%CI: 1.072–2.086, respectively), but not for the diffuse type and gastric cardia cancer (p > 0.05). CT/TT genotype for rs3732253 in the 3′ UTR was associated with increased risk of intestinal gastric cancer (adjusted OR = 1.464, 95%CI: 1.036–2.069), compared to their wild homozygous genotypes. These findings indicate that potentially functional TGF-α gene variant may contribute to the risk of intestinal gastric cancer and/or gastric noncardia cancer and could be used as molecular markers for detecting intestinal gastric cancer and/or gastric noncardia cancer in Chinese Han population.

Fruit and vegetable intake and the risk of gastric adenocarcinoma: A reanalysis of the european prospective investigation into cancer and nutrition (EPIC‐EURGAST) study after a longer follow‐up

In a previous European prospective investigation into cancer and nutrition (EPIC) analysis, we found an inverse association between total intake of vegetables, onion and garlic, and risk of intestinal gastric cancer (GC) and between citrus fruit and risk of cardia GC. The aim of this study is to reanalyze the effect of fruit and vegetables (F&V), based on a longer follow-up and twice the number of GC cases. Subjects are 477,312 men and women mostly aged 35 to 70 years participating in the EPIC cohort, including 683 gastric adenocarcinomas with 11 years of follow-up. Information on diet and lifestyle was collected at baseline. A calibration study in a subsample was used to correct for dietary measurement errors. When comparing the highest vs. lowest quintile of intake, we found an inverse association between total intake of V&F and GC risk [hazard ratio (HR) 0.77; 95% confidence interval (CI) 0.57-1.04; p for trend 0.02], between fresh fruit and risk of the diffuse type (HR 0.59; 95% CI 0.36-0.97; p for trend 0.03) and an inverse association between citrus fruit and risk of cardia cancer (HR 0.61; 95% CI 0.38-1.00, p for trend 0.01). Although calibration revealed somewhat stronger inverse associations, none of the risks reached statistical significance. There was no association between total or specific vegetables intake and GC risk. The inverse association between fresh fruit and citrus fruits and risk of GC seems to be restricted to smokers and the Northern European countries. Fresh fruit and citrus fruit consumption may protect against diffuse and cardia GC, respectively.

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>G, -819T>C, -592A>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

Cell proliferation-related genetic polymorphisms and gastric cancer risk: systematic review and meta-analysis

Apart from Helicobacter pylori infection and lifestyle factors, host genetic susceptibility has been suggested to contribute to individual variation in gastric cancer risk as well. Aiming to evaluate the associations between host cell proliferation-related genetic polymorphisms and gastric cancer susceptibility, we reviewed the related studies published until 15 September 2008 and quantitatively summarized the associations of the most widely studied polymorphisms (TP53 Arg72Pro, L-myc EcoRI) using meta-analysis. Fifty-five eligible studies were included in this review. Twenty-three polymorphisms significantly related to gastric cancer risk in at least one study were identified. Polymorphisms determining higher levels of growth factors, which are important for tissue repair, were recently observed to be associated with reduced risk of gastric cancer. In the meta-analysis, TP53 72Pro was associated with increased risk of diffuse gastric cancer among Asians (OR, 1.44; 95% CI, 1.04-1.99), but decreased risk of intestinal gastric cancer among Caucasians (OR, 0.56; 95% CI, 0.36-0.89). This review suggests that cell proliferation-related genetic polymorphisms could be candidate biomarkers of gastric cancer risk, but current evidence for the use for risk stratification is still very limited. Modestly significant associations in meta-analyses stratified by population or type of gastric cancer may be observed by chance because of the limited number of studies and small sample size. Larger studies are warranted to clarify the effect of cell proliferation-related genetic polymorphisms on gastric carcinogenesis.

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in gastric cancer of intestinal and diffuse histotypes.

In the present study we investigated the potential role of Toll-like receptor 4 (TLR-4) Asp299Gly and Thr399Ile polymorphisms as risk factors in the development of gastric cancer. TLR-4 Asp299Gly and Thr399Ile polymorphisms were investigated in 171 Italian patients with sporadic gastric cancer and in 151 controls. Unconditional regression (odds ratio and 95% confidence intervals) were used to investigate the association of the studied polymorphisms with gastric cancer. TLR-4 Thr399Ile polymorphism is linked with an increased susceptibility to gastric cancer (P = 0.023 and hazard ratio = 3.62). No significant association for TLR-4 Asp299Gly polymorphism was found. In the subgroup of patients with intestinal-type gastric cancer, a significant risk of gastric cancer was associated with TLR-4 Thr399Ile genotype (P = 0.006). Our results demonstrated that TLR-4 Thr399Ile polymorphism is linked with an increased susceptibility to gastric cancer. An increased risk for intestinal gastric cancer in carriers of the TLR4 Thr399Ile allele was observed. Future epidemiological studies should consider the possible interactions between proinflammatory genotypes (such as TLR and interleukin-1R polymorphisms) and other risk factors for cancer such as dietary habits and/or exposure to environmental carcinogens.