Association between genetic polymorphisms of macrophage scavenger receptor 1 (MSR1) gene and risk of prostate cancer in the Health Professionals Follow-Up Study.

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Background. Macrophage scavenger receptor 1 (MSR1) is involved in atherosclerosis, Alzheimer's disease, host defense (e.g., inflammation, innate and adaptive immunity), oxidative stress, and apoptosis. Accumulating evidence suggests that chronic inflammation is a risk factor for prostate cancer. Association studies assessing the relationship between sequence variants of MSR1 and prostate cancer are inconsistent. We hypothesized that sequence variants of MSR1 were associated with prostate cancer risk. Methods. In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped three common (>5%) single nucleotide polymorphisms (SNPs) discovered in a resequencing study spanning MSR1 to test for the association between sequence variants in this gene and prostate cancer risk. Results. Neither MSR1 SNPs nor estimated haplotypes were associated with prostate cancer risk (P value for the global test for haplotypes= 0.89). Among non-carriers of variant haplotype ACC, a family history of prostate cancer was significantly associated with prostate cancer risk (odds ratio (OR) = 1.53, 95% confidence interval (CI)=1.14-2.05): the effect of family history was not apparent among carriers of the ACC haplotype (P for interaction=0.20). MSR SNPs also did not appear to be associated with higher-grade or advanced stage prostate cancer. Conclusion. The association between sequence variants of MSR1 and the risk of prostate cancer was null. The suggestive but insignificant interaction with family history needs replication in other datasets. Further study of aggressive prostate cancer may be warranted as we had limited power to assess these.