Analysis of recently identified prostate cancer susceptibility loci in a population-based study: associations with family history and clinical features.
OBJECTIVE
Two recent genome-wide association studies have highlighted several single nucleotide polymorphisms (SNPs) purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and the clinicopathologic features of the disease.


METHODS
We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk stratified by family history of prostate cancer and clinicopathologic features of the disease was calculated with the use of logistic and polytomous regression.


RESULTS
These results confirm the importance of multiple, previously reported SNPs in relation to prostate cancer susceptibility; 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude with that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, whereas risk estimates for rs10993994 and rs5945619 varied by Gleason score.


CONCLUSIONS
Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however, the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features.
National Human Genome Research Institute, Cancer Genetics Branch, NIH, Bethesda, MD, USA.
Liesel M
LM
Fitzgerald
Erika M
EM
Kwon
Joseph S
JS
Koopmeiners
Claudia A
CA
Salinas
Janet L
JL
Stanford
Elaine A
EA
Ostrander
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D015996:Survival Rate