title: 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 cells and linkage studies in families affected with hereditary prostate cancer (HPC) 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 carcinogenesis. 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.
authors.affiliation: Center for Human Genomics and the Department of Public Health, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Akira
authors.initials: A
authors.lastname: Komiya
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Isaacs
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hu
authors.forename: David
authors.initials: D
authors.lastname: Sterling
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hawkins
authors.forename: Aubrey
authors.initials: A
authors.lastname: Turner
authors.forename: Charles M
authors.initials: CM
authors.lastname: Ewing
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Faith
authors.forename: Jill R
authors.initials: JR
authors.lastname: Johnson
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Piroska
authors.initials: P
authors.lastname: Bujnovszky
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Wiley
authors.forename: Angelo M
authors.initials: AM
authors.lastname: DeMarzo
authors.forename: G Steven
authors.initials: GS
authors.lastname: Bova
authors.forename: Baoli
authors.initials: B
authors.lastname: Chang
authors.forename: M Craig
authors.initials: MC
authors.lastname: Hall
authors.forename: David L
authors.initials: DL
authors.lastname: McCullough
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Vahan S
authors.initials: VS
authors.lastname: Kassabian
authors.forename: John D
authors.initials: JD
authors.lastname: Carpten
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: Jill
authors.initials: J
authors.lastname: Ohar
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Walsh
authors.forename: William B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D044383:Black People / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D005819:Genetic Markers; C495139:MSR1 protein, human; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A