Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)

Abstract

Background: The MHC class I chain-related protein A (MICA) cancer risk (312 colorectal cancers, 10,834 participants). In genetic and protein B (MICB) participate in tumor immunosurveillance analyses, estimates adjusted for ancestry markers were meta- and may be important in colorectal cancer, but have not been analyzed. examined in colorectal cancer development. Results: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-Methods: sMICA and sMICB blood levels were measured by A, rs2596542-T, and rs2395029-G were significantly associated with SomaScan in Visit 2 (1990–92, baseline) and Visit 3 (1993–95) decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and samples in cancer-free participants in the Atherosclerosis Risk in MICB, was also associated with increased sMICB levels. Rs2596542-Communities Study. We selected rs1051792, rs1063635, rs2516448, T was significantly associated with decreased colorectal cancer risk. rs3763288, rs1131896, rs2596542, and rs2395029 that were located Lower sMICA levels were associated with lower colorectal cancer in or in the vicinity of MICA or MICB and were associated with risk in males (HR ¼ 0.68; 95% confidence interval, 0.49–0.96) but cancer or autoimmune diseases in published studies. SNPs were not in females (Pinteraction ¼ 0.08). genotyped by the Affymetrix Genome-Wide Human SNP Array. Conclusions: Rs2596542-T associated with lower sMICA levels We applied linear and Cox proportional hazards regressions to was associated with decreased colorectal cancer risk. Lower sMICA examine the associations of preselected SNPs with sMICA and levels were associated with lower colorectal cancer risk in males. sMICB levels and colorectal cancer risk (236 colorectal cancers, Impact: These findings support an importance of immunosur-8,609 participants) and of sMICA and sMICB levels with colorectal veillance in colorectal cancer.