Polymorphisms in Th1/Th2 cytokine genes, hormone replacement therapy, 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 hormone replacement therapy (HRT) and risk of non-Hodgkin lymphoma (NHL). Compared to women without a history of HRT use, women with a history of HRT use had a significantly decreased risk of NHL if they carried IFNGR2 (rs1059293) CT/TT genotypes (OR=0.5, 95%CI: 0.3-0.9), IL13 (rs20541) GG genotype (OR=0.6, 95%CI: 0.4-0.9) and IL13 (rs1295686) CC genotype (OR=0.6, 95%CI: 0.4-0.8), but not among women who carried IFNGR2 CC, IL13 AG /AA and IL13 CT/TT genotypes. A similar pattern was also observed for B-cell lymphoma but not for T-cell lymphoma. A statistically significant interaction was observed for IFNGR2 (rs1059293 Pforinteraction=0.024), IL13 (rs20541 Pforinteraction=0.005), IL13 (rs1295686 Pforinteraction=0.008) and IL15RA (rs2296135 Pforinteraction=0.049) for NHL overall; IL13 (rs20541 Pforinteraction=0.0009), IL13 (rs1295686 Pforinteraction=0.0002), and IL15RA (rs2296135 Pforinteraction=0.041) for B-cell lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between HRT and NHL risk.