Meta-analysis of association of rare mutations and common sequence variants in the MSRI gene and prostate cancer risk

BACKGROUND. MSR1 has been reported to be associated with increased risk of prostate cancer (PCa). METHODS. We performed a meta-analysis of all eight published studies to evaluate the pooled effect of three rare mutations (R293X, S41T, and D174Y) and five common sequence variants (PROS, INDEL1, IVS5-59, P275A, and INDEL7), stratified by race and sporadic/hereditary cancer. RESULTS. Several variants were significantly or marginally significantly associated with sporadic, not hereditary PCa risk, including R293X in white men (random effect OR = 1.34, P = 0.09) and D174Y inblack men (random effect OR = 2.41, P = 0.04). The associations were not significant when the initial study was excluded. However, the frequency of the D174Y mutation was consistently higher among cases in all three studies that examined black men. CONCLUSIONS. Overall, this meta-analysis suggests the MSR1 gene does not independently confer a major risk to PCa but may confer a moderate risk to PCa, especially in black men.