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

• Published in: Carcinogenesis (New York) Vol. 28; no. 1; pp. 118 - 123
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.2007; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Case-Control Studies; Epidemiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Genetic Predisposition to Disease; Genotype; Helicobacter pylori; Humans; Interleukin-12 Subunit p35 - genetics; Male; Medical sciences; Middle Aged; Odds Ratio; Poland; Polymorphism, Single Nucleotide - genetics; Public health. Hygiene; Public health. Hygiene-occupational medicine; Receptors, Interferon - genetics; Risk Factors; Smoking; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Th1 Cells - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumors; Poland; Genetic variability; Gene; Risk factor; Digestive diseases; Genotype; Genetics; Malignant tumor; Stomach cancer; Epidemiology; Gastric disease; Polymorphism
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgl130

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.