Genome-wide association study of prostate cancer identifies a second risk locus at 8q24.
Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).
Yeager
Meredith
M
SAIC-Frederick, National Cancer Institute (NCI)-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
Orr
Nick
N
Hayes
Richard B
RB
Jacobs
Kevin B
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Kraft
Peter
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Wacholder
Sholom
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Minichiello
Mark J
MJ
Fearnhead
Paul
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Yu
Kai
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Chatterjee
Nilanjan
N
Wang
Zhaoming
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Welch
Robert
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Staats
Brian J
BJ
Calle
Eugenia E
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Feigelson
Heather Spencer
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Thun
Michael J
MJ
Rodriguez
Carmen
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Albanes
Demetrius
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Virtamo
Jarmo
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Weinstein
Stephanie
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Schumacher
Fredrick R
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Giovannucci
Edward
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Willett
Walter C
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Cancel-Tassin
Geraldine
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Cussenot
Olivier
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Valeri
Antoine
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Andriole
Gerald L
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Gelmann
Edward P
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Tucker
Margaret
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Gerhard
Daniela S
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Fraumeni
Joseph F
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Hoover
Robert
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Hunter
David J
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Chanock
Stephen J
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Thomas
Gilles
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D001741:Black or African American; D001483:Base Sequence; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D023281:Genomics / Q000379:methods; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D014481:United States; D044465:White People