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 Hall & 11 others David 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

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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-genesis 5-10 . 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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Scavenger Receptors
Germ-Line Mutation
Prostatic Neoplasms
Genes
African Americans
Mutation
Nonsense Codon
Human Chromosomes
Missense Mutation
Prostate

Cite this

Xu, J., Lilly Zheng, S., Komiya, A., Mychaleckyj, J. C., Isaacs, S. D., Hu, J. J., ... Meyers, D. A. (2002). Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Nature Genetics, 32(2), 321-325. https://doi.org/10.1038/ng994
Xu, Jianfeng ; Lilly Zheng, S. ; Komiya, Akira ; Mychaleckyj, Josyf C. ; Isaacs, Sarah D. ; Hu, Jennifer J. ; Sterling, David ; Lange, Ethan M. ; Hawkins, Gregory A. ; Turner, Aubrey ; Ewing, Charles M. ; Faith, Dennis A. ; Johnson, Jill R. ; Suzuki, Hiroyoshi ; Bujnovszky, Piroska ; Wiley, Kathleen E. ; DeMarzo, Angelo M. ; Steven Bova, G. ; Chang, Baoli ; Craig Hall, M. ; McCullough, David L. ; Partin, Alan W. ; Kassabian, Vahan S. ; Carpten, John D. ; Bailey-Wilson, Joan E. ; Trent, Jeffrey M. ; Ohar, Jill ; Bleecker, Eugene R. ; Walsh, Patrick C. ; Isaacs, William B. ; Meyers, Deborah A. / Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. In: Nature Genetics. 2002 ; Vol. 32, No. 2. pp. 321-325.
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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-genesis 5-10 . 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.",
author = "Jianfeng Xu and {Lilly Zheng}, S. and Akira Komiya and Mychaleckyj, {Josyf C.} and Isaacs, {Sarah D.} and Hu, {Jennifer J.} and David Sterling and Lange, {Ethan M.} and Hawkins, {Gregory A.} and Aubrey Turner and Ewing, {Charles M.} and Faith, {Dennis A.} and Johnson, {Jill R.} and Hiroyoshi Suzuki and Piroska Bujnovszky and Wiley, {Kathleen E.} and DeMarzo, {Angelo M.} and {Steven Bova}, G. and Baoli Chang and {Craig Hall}, M. and McCullough, {David L.} and Partin, {Alan W.} and Kassabian, {Vahan S.} and Carpten, {John D.} and Bailey-Wilson, {Joan E.} and Trent, {Jeffrey M.} and Jill Ohar and Bleecker, {Eugene R.} and Walsh, {Patrick C.} and Isaacs, {William B.} and Meyers, {Deborah A.}",
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Xu, J, Lilly Zheng, S, Komiya, A, Mychaleckyj, JC, Isaacs, SD, Hu, JJ, Sterling, D, Lange, EM, Hawkins, GA, Turner, A, Ewing, CM, Faith, DA, Johnson, JR, Suzuki, H, Bujnovszky, P, Wiley, KE, DeMarzo, AM, Steven Bova, G, Chang, B, Craig Hall, M, McCullough, DL, Partin, AW, Kassabian, VS, Carpten, JD, Bailey-Wilson, JE, Trent, JM, Ohar, J, Bleecker, ER, Walsh, PC, Isaacs, WB & Meyers, DA 2002, 'Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk', Nature Genetics, vol. 32, no. 2, pp. 321-325. https://doi.org/10.1038/ng994

Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. / Xu, Jianfeng; Lilly Zheng, S.; Komiya, Akira; Mychaleckyj, Josyf C.; Isaacs, Sarah D.; Hu, Jennifer J.; Sterling, David; Lange, Ethan M.; Hawkins, Gregory A.; Turner, Aubrey; Ewing, Charles M.; Faith, Dennis A.; Johnson, Jill R.; Suzuki, Hiroyoshi; Bujnovszky, Piroska; Wiley, Kathleen E.; DeMarzo, Angelo M.; Steven Bova, G.; Chang, Baoli; Craig Hall, M.; McCullough, David L.; Partin, Alan W.; Kassabian, Vahan S.; Carpten, John D.; Bailey-Wilson, Joan E.; Trent, Jeffrey M.; Ohar, Jill; Bleecker, Eugene R.; Walsh, Patrick C.; Isaacs, William B.; Meyers, Deborah A.

In: Nature Genetics, Vol. 32, No. 2, 01.10.2002, p. 321-325.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk

AU - Xu, Jianfeng

AU - Lilly Zheng, S.

AU - Komiya, Akira

AU - Mychaleckyj, Josyf C.

AU - Isaacs, Sarah D.

AU - Hu, Jennifer J.

AU - Sterling, David

AU - Lange, Ethan M.

AU - Hawkins, Gregory A.

AU - Turner, Aubrey

AU - Ewing, Charles M.

AU - Faith, Dennis A.

AU - Johnson, Jill R.

AU - Suzuki, Hiroyoshi

AU - Bujnovszky, Piroska

AU - Wiley, Kathleen E.

AU - DeMarzo, Angelo M.

AU - Steven Bova, G.

AU - Chang, Baoli

AU - Craig Hall, M.

AU - McCullough, David L.

AU - Partin, Alan W.

AU - Kassabian, Vahan S.

AU - Carpten, John D.

AU - Bailey-Wilson, Joan E.

AU - Trent, Jeffrey M.

AU - Ohar, Jill

AU - Bleecker, Eugene R.

AU - Walsh, Patrick C.

AU - Isaacs, William B.

AU - Meyers, Deborah A.

PY - 2002/10/1

Y1 - 2002/10/1

N2 - 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-genesis 5-10 . 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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