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Helicobacter pyloriinfection, the dominant risk factor for gastric cancers, has been shown to elicit T helper type 1 (Th1) polarized immunological responses. We conducted a population-based study of 305 gastric cancer cases and 427 age- and gender-matched controls in Warsaw, Poland, to evaluate the association with several variants in genes responsible for Th1-cell-mediated response. Genotyping was performed on genomic DNA by TaqManTMassays to determineTNFA(−308 G&gt;A, −417 G&gt;A, −555 G&gt;A, −1036 C&gt;T, −1042 C&gt;A, −1210 T&gt;C),IL1A(−889 C&gt;T),IFNGR2(Ex7-128 T&gt;C, Ex2-34 C&gt;G and Ex2-16 A&gt;G) andIL12A(IVS2-798 T&gt;A, IVS2-701 C&gt;A and Ex7+277 G&gt;A) polymorphisms. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for sex, age, education and smoking status. Out of six single nucleotide polymorphisms (SNPs) tested inTNFA, gastric cancer risk was significantly associated with theTNFA(−308 G&gt;A) polymorphism, with ORs of 1.4 (95% CI: 1.0–2.0) for the G/A and 2.5 (95% CI: 1.3–4.9) for the A/A genotype carriers, when compared with the more frequent genotype (G/G) (P-trend &lt; 0.001). Among the three tested SNPs in theIFNGR2gene, only the Ex7-128C&gt;T polymorphism was associated with increased risk, with ORs of 1.5 (95% CI: 1.0–2.3) for T/C and 1.7 (95% CI: 1.1–2.7) for C/C carriers when compared with T/T carriers (P-trend = 0.01). Subjects carrying bothIFNGR2Ex7-128 C/C andTNFA−308 A/A genotypes had the highest risk (OR = 5.5, 95% CI: 1.5–19.4), although the interaction was not statistically significant.IL1A(−889 C&gt;T) and the three examinedIL12Avariants were unrelated to gastric cancer risk. Our findings suggest that two Th1-related polymorphisms (TNFA−308 A&gt;G andIFNGR2Ex7-128 C&gt;T) may increase the risk of gastric cancer.

Polymorphisms in Th1-type cell-mediated response genes and risk of gastric cancer