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

Lifang 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, W. H. Chow

*Corresponding author for this work

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81 Scopus citations

Abstract

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 TaqMan TM 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 E×7+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.

Original languageEnglish (US)
Pages (from-to)118-123
Number of pages6
JournalCarcinogenesis
Volume28
Issue number1
DOIs
StatePublished - Jan 2007

ASJC Scopus subject areas

  • Cancer Research

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    Hou, L., El-Omar, E. M., Chen, J., Grillo, P., Rabkin, C. S., Baccarelli, A., Yeager, M., Chanock, S. J., Zatonski, W., Sobin, L. H., Lissowska, J., Fraumeni, J. F., & Chow, W. H. (2007). Polymorphisms in Th1-type cell-mediated response genes and risk of gastric cancer. Carcinogenesis, 28(1), 118-123. https://doi.org/10.1093/carcin/bgl130