MIC1 and IL1RN genetic variation and advanced prostate cancer risk.

Recently, polymorphisms in macrophage inhibitory cytokine-1 (MIC1) and interleukin 1 receptor antagonist (IL1RN) were identified to be associated with prostate cancer risk (1-3). MIC-1 is a divergent member of the transforming growth factor-h superfamily of cytokines. In the Cancer Prostate in Sweden study, the nonsynonymous MIC1 H6D polymorphism was associated with a lowered risk of prostate cancer [CG versus CC; odds ratio (OR), 0.80; 95% confidence interval (95% CI), 0.66-0.97; ref. 2], whereas an Australian study found this polymorphism associated with a nonsignificant lowered risk of prostate cancer (CG/GG versus CC; OR, 0.85; 95% CI, 0.701.04) yet an increased risk of prostate cancer death (CG/GG versus CC; OR, 1.72; 95% CI, 1.06-2.78; ref. 1). IL1RN inhibits the proinflammatory response of interleukin 1-a and interleukin 1-h cytokines. The IL1RN haplotype (ATGC) was significantly associated with prostate cancer risk in the Cancer Prostate in Sweden study (homozygous carriers versus noncarriers; OR, 1.6; 95% CI, 1.2-2.2), with larger effects observed among advanced disease (homozygous carriers versus noncarriers; OR, 1.8; 95% CI, 1.3-2.5; ref. 3). To further investigate these previous reports, we comprehensively surveyed the common genetic variation of MIC1 and IL1RN and tested whether inherited differences at these loci predispose men to advanced prostate cancer.