Journal Article

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

L. Hou, E.M. El-Omar, J. Chen, P. Grillo, C.S. Rabkin, A. Baccarelli, M. Yeager, S.J. Chanock, W. Zatonski, L.H. Sobin, J. Lissowska, J.F. Fraumeni and W.H. Chow

in Carcinogenesis

Volume 28, issue 1, pages 118-123
Published in print August 2006 | ISSN: 0143-3334
Published online January 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl130
Polymorphisms in Th1-type cell-mediated response genes and risk of gastric cancer

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Helicobacter pylori infection, 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 TaqManTM assays to determine TNFA (−308 G>A, −417 G>A, −555 G>A, −1036 C>T, −1042 C>A, −1210 T>C), IL1A (−889 C>T), IFNGR2 (Ex7-128 T>C, Ex2-34 C>G and Ex2-16 A>G) and IL12A (IVS2-798 T>A, IVS2-701 C>A and Ex7+277 G>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 in TNFA, gastric cancer risk was significantly associated with the TNFA (−308 G>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 < 0.001). Among the three tested SNPs in the IFNGR2 gene, only the Ex7-128C>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 both IFNGR2 Ex7-128 C/C and TNFA −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>T) and the three examined IL12A variants were unrelated to gastric cancer risk. Our findings suggest that two Th1-related polymorphisms (TNFA −308 A>G and IFNGR2 Ex7-128 C>T) may increase the risk of gastric cancer.

Journal Article.  4002 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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