Multiple regions within 8q24 independently affect risk for prostate cancer

Harvard University, Cambridge, Massachusetts, United States
Nature Genetics (Impact Factor: 29.65). 05/2007; 39(5):638-44. DOI: 10.1038/ng2015
Source: PubMed

ABSTRACT 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 variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.

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Available from: Daniel O Stram, Jul 07, 2015
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    • "First identified SNPs associated with PCa risk were located within the 8q24 chromosomal region [8-10]. Afterwards, a large number of other PCa risk loci were identified, many of which were replicated in different populations [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [34] [35] [36]. "
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    • "At least three distinct loci in separate linkage disequilibrium blocks are present on 8q24, all of which have been confirmed in subsequent genome-wide association studies (Gudmundsson et al, 2007; Yeager et al, 2007; Eeles et al, 2008; Thomas et al, 2008). Analyses by Haiman et al identified at least seven or more independent risk alleles in these blocks (Haiman et al, 2007). "
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    • "Recent studies have identified numerous single nucleotide polymorphisms (SNPs) that modify an individual's risk of developing prostate cancer (Amundadottir et al, 2006; Eeles et al, 2008; Gudmundsson et al, 2007a; Gudmundsson et al, 2008; Gudmundsson et al, 2007b; Haiman et al, 2007; Robbins et al, 2007; Thomas et al, 2008). Although some investigators have considered the possibility of heterogeneity between ethnic groups, where a SNP shows a different effect on prostate cancer risk depending on the population being studied, these studies only considered ethnic groups with different continents of ancestral origins (Haiman et al, 2007; Waters et al, 2009; Yamada et al, 2009; Hooker et al, 2010; Zheng et al, 2010). As alleles of numerous SNPs are known to vary in frequency across Europe (Bersaglieri et al, 2004), and population substructure is consistently observed in Americans with ancestry from different locations in Europe (Price et al, 2008; Tian et al, 2008), there is a possibility that prostate cancer risk alleles may have different effects in different populations of European ancestry. "
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