Prostate cancer risk-associated variants reported from genome-wide association studies: meta-analysis and their contribution to genetic Variation.
BACKGROUND
Genome-wide association studies (GWAS) have led to the discovery of multiple single nucleotide polymorphisms (SNPs) that are associated with prostate cancer (PCa) risk. These SNPs may potentially be used for risk prediction. To date, there is not a stable estimate of their effect on PCa risk and their contribution to the genetic variation both of which are important for future risk prediction.


METHODS
A literature review was conducted to identify SNPs associated with PCa risk with the following criteria: (1) GWAS in the Caucasian population; (2) SNPs with P-value <1.0×10(-6); and (3) one SNP from each independent LD block. A meta-analysis was performed to estimate combined odds ratio (OR) and its 95% confidence interval (CI) for the identified SNPs. The proportion of total genetic variance that is attributable by each of these SNPs was also estimated.


RESULTS
Thirty PCa risk-associated SNPs were identified. These SNPs had OR estimates between 1.12 and 1.47 except for marker rs16901979 (OR=1.80). Significant heterogeneity in OR estimates was found among different studies for 13 SNPs. The proportion of total genetic variance attributed by each SNP ranged between 0.2% and 0.9%. These 30 SNPs explained ∼13.5% of the total genetic variance of PCa risk in the Caucasian population.


CONCLUSIONS
This study provides more stable OR estimates for PCa risk-associated SNPs, which is an important baseline for the effect of these SNPs in risk prediction. These SNPs explain a considerable proportion of genetic variance, however, the majority of genetic variance has yet to be explained.
Kim
Seong-Tae
ST
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Cheng
Yu
Y
Hsu
Fang-Chi
FC
Jin
Tao
T
Kader
A Karim
AK
Zheng
S Lilly
SL
Isaacs
William B
WB
Xu
Jianfeng
J
Sun
Jielin
J
D016022:Case-Control Studies; D002874:Chromosome Mapping; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors