Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk

Abstract

Deletions on human chromosome 8p22–23 in prostate cancer cells1 and linkage studies in families affected with hereditary prostate cancer (HPC)2,3,4 have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis5,6,7,8,9,10. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.

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Figure 1: Pedigrees representing the 13 families with MSR1 mutations identified in this study (with minor changes in family structure to protect confidentiality).
Figure 2: Macrophage scavenger receptor 1.

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Acknowledgements

We thank all subjects for their participation; F. Torti for his support in recruiting study subjects at Wake Forest University School of Medicine; W. Catalona for measuring PSA concentrations in the asbestos study population; R. Gurganus, L. Mangold and D. Lamm for help in prostate cancer screenings; and J.L. Hicks for help with immunohistochemistry. This work was partially supported by US Public Health Service Prostate Cancer Specialized Programs of Research Excellence grant, grants from the US Department of Defense to W.B.I. and J.X., Association for the Cure of Cancer of the Prostate, the Fund for Research and Progress in Urology, Johns Hopkins University, Wake Forest Comprehensive Cancer Center and the William Thomas Gerrard, Mario Anthony Duhon, Jennifer and John Chalsty Professorship in Urology.

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Correspondence to William B. Isaacs.

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The authors declare no competing financial interests.

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