Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.
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.
Xu
Jianfeng
J
Center for Human Genomics and the Department of Public Health, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Zheng
S Lilly
SL
Komiya
Akira
A
Mychaleckyj
Josyf C
JC
Isaacs
Sarah D
SD
Hu
Jennifer J
JJ
Sterling
David
D
Lange
Ethan M
EM
Hawkins
Gregory A
GA
Turner
Aubrey
A
Ewing
Charles M
CM
Faith
Dennis A
DA
Johnson
Jill R
JR
Suzuki
Hiroyoshi
H
Bujnovszky
Piroska
P
Wiley
Kathleen E
KE
DeMarzo
Angelo M
AM
Bova
G Steven
GS
Chang
Baoli
B
Hall
M Craig
MC
McCullough
David L
DL
Partin
Alan W
AW
Kassabian
Vahan S
VS
Carpten
John D
JD
Bailey-Wilson
Joan E
JE
Trent
Jeffrey M
JM
Ohar
Jill
J
Bleecker
Eugene R
ER
Walsh
Patrick C
PC
Isaacs
William B
WB
Meyers
Deborah A
DA
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
D005819:Genetic Markers; C495139:MSR1 protein, human; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A