Sequence variants at 22q13 are associated with prostate cancer risk.
To search for genetic variants that are associated with prostate cancer risk in the genome, we combined the data from our genome-wide association study (GWAS) in a population-based case-control study in Sweden with publicly available GWAS data from the Cancer Genetic Markers of Susceptibility (CGEMS) study. We limited the cases to those with aggressive disease in an attempt to identify risk variants that are associated with this most clinically relevant form of the disease. Among the most likely candidate single nucleotide polymorphisms (SNP) identified from the two GWAS, we sequentially confirmed one SNP at 22q13 in two independent study populations: the remaining subjects in Cancer of the Prostate in Sweden and a hospital-based case-control study at Johns Hopkins Hospital. Association of aggressive prostate cancer with the SNP at 22q13 was also observed in the publicly available data of four additional study populations from the second stage of the CGEMS study. In all seven study populations examined, the frequency of allele "C" of rs9623117 at 22q13 was consistently higher in aggressive cases than in controls. The combined allelic test was highly significant, with P = 5.0 x 10(-7). The odds ratio (OR) of allele C for aggressive prostate cancer was estimated to be 1.18 [95% confidence interval (95% CI), 1.11-1.26]. However, the SNP was also associated with nonaggressive prostate cancer, with an estimated OR of 1.11 (95% CI, 1.04-1.19; P = 0.004). The risk-associated variants are located within the genomic region of TNRC6B, a gene involved in miRNA-mediated mRNA degradation. Additional studies are warranted to further confirm the association.
Sun
Jielin
J
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Zheng
Siqun Lilly
SL
Wiklund
Fredrik
F
Isaacs
Sarah D
SD
Li
Ge
G
Wiley
Kathleen E
KE
Kim
Seong-Tae
ST
Zhu
Yi
Y
Zhang
Zheng
Z
Hsu
Fang-Chi
FC
Turner
Aubrey R
AR
Stattin
Pär
P
Liu
Wennuan
W
Kim
Jin Woo
JW
Duggan
David
D
Carpten
John
J
Isaacs
William
W
Grönberg
Henrik
H
Xu
Jianfeng
J
Chang
Bao-Li
BL
D000483:Alleles; D016022:Case-Control Studies; D002892:Chromosomes, Human, Pair 22; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*