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

Jianfeng Xu, S. Lilly Zheng, Akira Komiya, Josyf C. Mychaleckyj, Sarah D. Isaacs, Jennifer J. Hu, David Sterling, Ethan M. Lange, Gregory A. Hawkins, Aubrey Turner, Charles M. Ewing, Dennis A. Faith, Jill R. Johnson, Hiroyoshi Suzuki, Piroska Bujnovszky, Kathleen E. Wiley, Angelo M. DeMarzo, G. Steven Bova, Baoli Chang, M. Craig HallDavid L. McCullough, Alan W. Partin, Vahan S. Kassabian, John D. Carpten, Joan E. Bailey-Wilson, Jeffrey M. Trent, Jill Ohar, Eugene R. Bleecker, Patrick C. Walsh, William B. Isaacs, Deborah A. Meyers

Research output: Contribution to journalArticle

263 Scopus citations

Abstract

Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC)2-4 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 carcino-genesis5-10. 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.

Original languageEnglish
Pages (from-to)321-325
Number of pages5
JournalNature Genetics
Volume32
Issue number2
DOIs
StatePublished - 1 Oct 2002

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