Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma

Abstract

We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m², women with BMI more than or equal to 25 kg/m² had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 P_{forinteraction} = .034) and IL7R (rs1494555 P_{forinteraction} = .016) for NHL overall; IL7R (rs1494555 P_{forinteraction} = .016) and TNF (1799724 P_{forinteraction} = .031) for B-cell lymphoma; and IL5 (rs2069812 P_{forinteraction} = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 P_{forinteraction} = .006), IL13 (rs20541 P_{forinteraction} = .019), and IL7R (rs1494555 P_{forinteraction} = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 P_{forinteraction} = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 P_{forinteraction} = .013) and TNF (1799724 P_{forinteraction} = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.