Prostate cancer risk associated loci in African Americans.
Four genome-wide association studies, all in populations of European descent, have identified 20 independent single nucleotide polymorphisms (SNP) in 20 regions that are associated with prostate cancer risk. We evaluated these 20 SNPs in a combined African American (AA) study, with 868 prostate cancer patients and 878 control subjects. For 17 of these 20 SNPs, implicated risk-associated alleles were found to be more common in these AA cases than controls, significantly more than expected under the null hypothesis (P = 0.03). Two of these 17 SNPs, located at 3p12, and region 2 at 8q24, were significantly associated with prostate cancer risk (P < 0.05), and only SNP rs16901979 at region 2 of 8q24 remained significant after accounting for 20 tests. A multivariate analysis of additional SNPs across the broader 8q24 region revealed three independent prostate cancer risk-associated SNPs, including rs16901979, rs13254738, and rs10086908. The first two SNPs were approximately 20 kb apart and the last SNP, a novel finding from this study, was approximately 100 kb centromeric to the first two SNPs. These results suggest that a systematic evaluation of regions harboring known prostate cancer risk SNPs implicated in other races is an efficient approach to identify risk alleles for AA. However, studies with larger numbers of AA subjects are needed, and this will likely require a major collaborative effort to combine multiple AA study populations.
Xu
Jianfeng
J
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. jxu@wfubmc.edu
Kibel
Adam S
AS
Hu
Jennifer J
JJ
Turner
Aubrey R
AR
Pruett
Kristen
K
Zheng
Siqun Lilly
SL
Sun
Jielin
J
Isaacs
Sarah D
SD
Wiley
Kathleen E
KE
Kim
Seong-Tae
ST
Hsu
Fang-Chi
FC
Wu
William
W
Torti
Frank M
FM
Walsh
Patrick C
PC
Chang
Bao-Li
BL
Isaacs
William B
WB
D001741:Black or African American / Q000235:genetics*; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics