Data from Associations between MICA and MICB genetic variants, protein levels, and colorectal cancer: Atherosclerosis Risk in Communities (ARIC)

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