Macrophage scavenger receptor 1 999C>T (R293X) mutation and risk of prostate cancer.
BACKGROUND
Variants in the gene encoding the macrophage scavenger receptor 1 (MSR1(4)) protein have been identified in men with prostate cancer, and several small studies have suggested that the 999C>T (R293X) protein-truncating mutation may be associated with an increased risk for this disease.


METHODS
Using large case-control, cohort, and prostate cancer family studies conducted in several Western countries, we tested for the 999C>T mutation in 2,943 men with invasive prostate carcinoma, including 401 males from multiple-case families, 1,982 cases unselected for age, and 575 men diagnosed before the age of 56 years, and in 2,870 male controls. Risk ratios were estimated by unconditional logistic regression adjusting for country and by a modified segregation analysis. A meta-analysis was conducted pooling our data with published data.


RESULTS
The prevalence of MSR1*999C>T mutation carriers was 0.027 (SE, 0.003) in cases and 0.022 (SE, 0.002) in controls, and did not differ by country, ethnicity, or source. The adjusted risk ratio for prostate cancer associated with being a 999C>T carrier was 1.31 [95% confidence interval (CI), 0.93-1.84; P = 0.16]. The modified segregation analysis estimated the risk ratio to be 1.20 (95% CI, 0.87-1.66; P = 0.16). The risk ratio estimated from the meta-analysis was 1.34 (95% CI, 0.94-1.89; P = 0.10).


CONCLUSIONS
Our large-scale analysis of case and controls from several countries found no evidence that the 999C>T mutation is associated with increased risk of prostate cancer. The meta-analysis suggests it is unlikely that this mutation confers more than a 2-fold increased risk.
Hope
Questa
Q
Translational Cancer Genetics Team, Section of Cancer Genetics and Urology Unit, Male Urological Centre and Institute of Cancer Research and Royal Marsden NHS Trust, Surrey, United Kingdom.
Bullock
Sarah
S
Evans
Christopher
C
Meitz
Julia
J
Hamel
Nancy
N
Edwards
Stephen M
SM
Severi
Gianluca
G
Dearnaley
David
D
Jhavar
Sameer
S
Southgate
Christine
C
Falconer
Alison
A
Dowe
Anna
A
Muir
Kenneth
K
Houlston
Richard S
RS
Engert
James C
JC
Roquis
David
D
Sinnett
Daniel
D
Simard
Jacques
J
Heimdal
Ketil
K
Møller
Pål
P
Maehle
Lovise
L
Badzioch
Michael
M
Eeles
Rosalind A
RA
Easton
Douglas F
DF
English
Dallas R
DR
Southey
Melissa C
MC
Hopper
John L
JL
Foulkes
William D
WD
Giles
Graham G
GG
D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D051116:Receptors, Scavenger; D012307:Risk Factors; D051117:Scavenger Receptors, Class A
C495139:MSR1 protein, human; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A