Modifying Effects of IL‐6 Polymorphisms on Body Size–Associated Breast Cancer Risk

Abstract
Objective: The association between obesity and breast cancer risk is complex. We examined whether the association between body size and breast cancer risk is modified by interleukin‐6 (IL6) genotype. Methods and Procedures: Five polymorphisms in the IL‐6 gene (rs1800797/‐596A>G, rs1800796/‐572G>C, rs1800795/‐174G>C, rs2069832/IVS2G>A, and rs2069849 exon 5 C>T) were studied. We investigated IL6 genotypes and haplotypes with indicators of body size among non‐Hispanic white (NHW) and Hispanic/American Indian (AI) breast cancer cases and controls living in the Southwestern United States. Results: We observed lower mean levels of BMI among NHW women who carried one or two copies of the GGCAC haplotype (in order: rs1800797, rs1800796, rs1800795, rs2069832, and rs2069849; P trend 0.02). This haplotype, with an estimated frequency of 43% in NHW study controls, was considerably less common in Hispanic/AI controls (19%). We did not detect significant interactions between IL6 genotypes or haplotypes and BMI categorized as low/normal (0.9 and the rs1800795 GG genotype had a greater than threefold increased risk of breast cancer (odds ratios (ORs) 3.22, 95% confidence intervals (CIs) 1.27, 817) when compared with women with a WHR P interaction 0.01). Discussion: These data suggest that IL‐6 genotypes may influence breast cancer risk in conjunction with central adiposity.

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