| Objective: Gastric cancer is the leading cause of cancer-related death in China. Gastric cancer has usually been considered as highly environmental disease by many epidemiological studies, but hostsusceptibility factors play an important role in cancer development. Host genetic factors, including interleukin-6 (IL-6) gene polymorphism, play a crucial role in the genetic predisposition to gastric cancer. A new important promoter variant of IL-6-6331 was identified to be associated with IL-6 production. The aim of this study was to investigate the association of IL-6-6331 polymorphisms with susceptibility to gastric cancer in a Chinese population.Methods: The study was performed in 375 patients with gastric cancer and 386 age- and gender-matched healthy controls. The total patients were diagnosed by histopathology,Genomic DNA was extracted from paraffin-embedded tissues of 500 gastric cancers using QIAamp DNA Mini Kit (Qiagen, Germany) and from 2 ml peripheral blood of 500 healthy controls using Gentra Puregene Blood Kit (Gentra Systems, Inc., Minneapolis, MN). IL-6 gene polymorphism was analyzed by PCR-based restriction fragment length polymorphism. DNA sequencing analysis of Random sample was used to confirm the results of IL-6 genotype. The influence of individual variants on gastric cancer risk was assessed usingχ2-tests. Associations between genotypic distributions and clinicopathologic features were analyzed using univariate tests, multivariate logistic regression modeling. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated and all statistical tests were two sided.Results: 1 After adjustment for the potential confounding effects of gender, age, IL-6-6331TC genotype was associated with a decreased risk of gastric cancer compared with the CC genotype [adjusted Odds ratio (OR) = 0.37, 95% confidence interval (CI) = 1.15-0.94]. The overall T carriers (either TC or TT) were associated with a marginally lower gastric cancer risk when compared with CC carriers (OR=0.42, P=0.060, 95% CI: 0.17-1.04).2 Further stratification analyses indicated that the protective effect of TC genotype was especially noteworthy in poorly differentiated gastric cancer (adjusted OR = 0.36, 95% CI 0.13– 0.97), non-cardia gastric cancer (adjusted OR = 0.38, 95% CI 0.14– 1.02) and intestinal type gastric cancer (adjusted OR = 0.39, 95% CI 0.15– 1.02). The association between genotype and moderately or well differentiated gastric cancer, and mix or diffuse type gastric cancer, however, were not significant.3 We evaluated the role of IL-6-6331 polymorphism in gastric cancer according to the TNM tumor staging, carriers of TC genotype showed decreased risk for developing large tumor size at stage III/IV gastric cancers compared to the CC genotype (OR: 0.34, 95% CI: 0.13-0.88). Moreover, carriers of TC or TT genotype were associated decreased risk for lymph node metastasis with Ors of 0.30 (95% CI=0.12-0.79) and 0.35 (95% CI: 0.14-0.89, P=0.028) compared to the CC genotype, respectively. No association between TC carriers and the risk of tumor metastasis was found. However, carriers of TT genotype showed decreased risk for tumor metastasis(OR=0.22, 95% CI=0.06- 0.82) compared to the CC genotype.4 Compared with the CC, we found that the associated with the IL-6-6331TC and TT alleles was less frequent in the age group of 40-65. (OR=0.16, 95% CI=0.03-0.76) and (OR=0.20, 95% CI=0.04-0.91), respectively. The associations were not statistically significant in the two other age groups(age≦40 and≧65). When stratified by age, we did not observe any significant differences in the gender.5 No significant relationship was observed between the IL-6-6331 polymorphism and survival of gastric cancer patients. Meanwile, Overall survival of the gastric cancer patients was analyzed for dependence on IL-6-6331 genotypes using Kaplan-Meier survival curves. There was no statistically difference among different IL-6-6331 genotypes.Conclusion: 1 IL-6-6331TC genotype was associated with decreased risk of gastric cancer( P=0.036); These results suggest that the IL-6-6331 polymorphism involved in susceptibility to developing gastric cancer.2 The overall T carriers (either TC or TT) were associated with a marginally lower gastric cancer risk when compared with CC carriers (P=0.060).3 IL-6-6331TC genotype showed a reduced risk of poorly differentiated gastric cancer ( P=0.043).4 carriers of TC genotype showed trend toward a decreased risk for developing non-cardiac gastric cancer of marginal statistical significance(P=0.055).5 TC genotype was associated with a marginally significant reduced risk of intestinal-type of gastric cancer (P=0.055).6 Compared to the CC genotype, carriers of TC genotype showed decreased risk for developing large tumor size at stage III/IV gastric cancers (P=0.026).7 IL-6-6331TC and TT alleles was less frequent in the age group of 40-65 (P=0.021) and (P=0.038), respectively.
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