Multiple regions within 8q24 independently affect risk for prostate cancer.
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ABSTRACT:
SUBMITTER: Haiman CA
PROVIDER: S-EPMC2638766 | biostudies-literature | 2007 May
REPOSITORIES: biostudies-literature
Publications
Multiple regions within 8q24 independently affect risk for prostate cancer.
Haiman Christopher A CA Patterson Nick N Freedman Matthew L ML Myers Simon R SR Pike Malcolm C MC Waliszewska Alicja A Neubauer Julie J Tandon Arti A Schirmer Christine C McDonald Gavin J GJ Greenway Steven C SC Stram Daniel O DO Le Marchand Loic L Kolonel Laurence N LN Frasco Melissa M Wong David D Pooler Loreall C LC Ardlie Kristin K Oakley-Girvan Ingrid I Whittemore Alice S AS Cooney Kathleen A KA John Esther M EM Ingles Sue A SA Altshuler David D Henderson Brian E BE Reich David D
Nature genetics 20070401 5
After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The ...[more]
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Project description:Recent studies based on genome-wide association, linkage, and admixture scan analysis have reported associations of various genetic variants in 8q24 with susceptibility to breast, prostate, and colorectal cancer. This locus lies within a 1.18-Mb region that contains no known genes but is bounded at its centromeric end by FAM84B and at its telomeric end by c-MYC, two candidate cancer susceptibility genes. To investigate the associations of specific loci within 8q24 with specific cancers, we genotyped the nine previously reported cancer-associated single-nucleotide polymorphisms across the region in four case-control sets of prostate (1854 case subjects and 1894 control subjects), breast (2270 case subjects and 2280 control subjects), colorectal (2299 case subjects and 2284 control subjects), and ovarian (1975 case subjects and 3411 control subjects) cancer. Five different haplotype blocks within this gene desert were specifically associated with risks of different cancers. One block was solely associated with risk of breast cancer, three others were associated solely with the risk of prostate cancer, and a fifth was associated with the risk of prostate, colorectal, and ovarian cancer, but not breast cancer. We conclude that there are at least five separate functional variants in this region.
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