Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations.
BACKGROUND
A strong cumulative effect of five genetic variants and family history on prostate cancer risk was recently reported in a Swedish population (CAPS). We carried out this study to confirm the finding in two U.S. study populations and perform a combined analysis to obtain a more stable estimate of the odds ratio (OR) for prostate cancer.


METHODS
We evaluated three SNPs at 8q24 and one SNP each at 17q12 and 17q24.3 in two study populations in the U.S. The first was a hospital-based case-control study population at Johns Hopkins Hospital (JHH), including 1,563 prostate cancer patients and 576 control subjects. The second was the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) Initiative, including 1,172 prostate cancer patients and 1,157 control subjects.


RESULTS
We confirmed a cumulative effect of five risk variants on prostate cancer risk. Based on a total of 5,628 cases and 3,514 controls from JHH, CGEMS, and CAPS, men who carry any combination of 1, 2, 3, and 4 or more of these five risk variants have an estimated OR (95% CI) of 1.41 (1.20-1.67), 1.88 (1.59-2.22), 2.36 (1.95-2.85), and 3.80 (2.77-5.22) for prostate cancer, respectively, compared to men who do not have any of these five risk variants. When family history was included, the cumulative effect was stronger.


CONCLUSIONS
These results provide an important confirmation for the cumulative effect of five genetic risk variants on prostate cancer risk. The more stable OR estimates of the cumulative effect of these six risk factors are a major step toward individual risk characterization for this disease.
Sun
Jielin
J
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Chang
Bao-Li
BL
Isaacs
Sarah D
SD
Wiley
Kathleen E
KE
Wiklund
Fredrik
F
Stattin
Pär
P
Duggan
David
D
Carpten
John D
JD
Trock
Bruce J
BJ
Partin
Alan W
AW
Walsh
Patrick C
PC
Grönberg
Henrik
H
Xu
Jianfeng
J
Isaacs
William B
WB
Zheng
S Lilly
SL
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014481:United States / Q000453:epidemiology
D014408:Biomarkers, Tumor