Genetic variation in proinflammatory cytokines IL6, IL6R, TNF-region, and TNFRSF1A and risk of breast cancer

Proinflammatory cytokines are associated with age-related diseases including arthritis and heart disease. IL6 and TNF also play key roles in estrogen modulation in older women. We explored whether variation in IL6 and TNF genes influenced the risk of breast cancer in samples that differed by age group: T alleles at IL6 rs2069861 among subjects in the oldest age group (OR 1.8, 95% CI 1.1–2.9), but no overall increased risk of breast cancer associated with any IL6 or IL6R variants in the combined data. There were significantly elevated risks of breast cancer among women 45–64 years old associated with a UTR 5′ flanking SNP LTA rs2009658 C>G allele (OR 1.5, 95% CI 1.1–1.9) and a nonsynonomous coding SNP TNFRSF1A rs767455 T>C allele (OR 1.3, 95% CI 1.1–1.6); these two variants were also elevated in the combined data (OR 1.3, 95% CI 1.1–1.5 and OR 1.2, 95% CI 1.1–1.4, respectively). This study supports a modest association between a variant in IL6 and breast cancer among older women and TNF-related variants and breast cancer among middle-aged women. Further evaluation of these genes in other studies is warranted.