Article

Germ-line mutations of the macrophage scavenger receptor 1 gene: association with prostate cancer risk in African-American men.

Department of Urology, University of Michigan, Medical School, Ann Arbor, Michigan 48109-0946, USA.
Cancer Research (Impact Factor: 9.28). 08/2003; 63(13):3486-9.
Source: PubMed

ABSTRACT Both rare germ-line mutations and common sequence variants of the macrophage scavenger receptor 1 (MSR1) gene have recently been implicated as potential prostate cancer susceptibility factors. However, existing studies are limited by the referral-based nature of samples and a paucity of African-American participants. In this context, we evaluated the association of germ-line mutations and common MSR1 sequence variants with prostate cancer risk in a case control study of a community-based sample of 134 African-American men with prostate cancer and 340 unaffected controls. In our sample, the rare Asp174Tyr missense change was identified nearly twice as frequently in men with prostate cancer (6.8%) compared with unaffected controls (3.6%; P = 0.14). Moreover, significantly different allele frequencies between cases and controls were observed for one of the sequence variants, IVS5-59 (P = 0.02). Taken together, our results provide some additional support for the hypothesis that selected, rare MSR1 mutations are associated with increased prostate cancer susceptibility among African-American men.

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    ABSTRACT: Familial history is one of the strongest risks factor for prostate cancer. One of the prostate cancer candidate genes is the CYP17 gene. A thymidine (T) to cytosine (C) transition (designated A2 variant) in the promoter region of the CYP17 gene has been used in several studies in order to determine a possible association with the prostate cancer risk. A recent meta-analysis found no effect of the CYP17 polymorphism for the sporadic prostate cancer. The question still remained unresolved for familial cases. In order to evaluate the role of the CYP17 A2 allele in familial aggregation of prostate cancer we performed an association study. In our study we realized a slight difference of CYP17 genotypes between sporadic cases and controls, but this unequal distribution was not significant. Our results showed no evidence that the CYP17 genotype might predispose for a familial aggregation of prostate cancer. Our results do not suggest a role of CYP17 as a high-risk susceptibility gene for familial prostate cancer nor as a modifier for the disease risk. Rare germline mutations of the macrophage scavenger receptor 1 (MSR1) gene were reported to be associated with prostate cancer risk in families with hereditary prostate cancer (HPC) and in probands with non-HPC. For the purpose of our study 6 length polymorphisms that span approximately 70kb of the MSR1 gene were used. One of the markers (IVS6 marker) was not in the HWE, so it was excluded from the further analysis. The results gained from analysing the five length polymorphisms did not lead to overall significant results concerning the allele and haplotype frequency distribution between the cases and controls. Some allelic transmission imbalance was seen in the INDEL1 marker when families were analysed with family-based association approach. Taken together our results do not support MSR1 as a high-risk gene for prostate cancer.
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