Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Nat Genet. 2011 Oct 9;43(11):1114-8. doi: 10.1038/ng.958.
We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.
我们对 2168 名澳大利亚黑色素瘤患者和 4387 名对照个体进行了全基因组关联研究。在这一发现阶段，我们确认了 MC1R、ASIP 和 MTAP-CDKN2A 等几个先前确定的黑色素瘤相关基因座。我们选择了九个基因座的变异体，在三个独立的病例对照研究中进行了复制（欧洲：2804 名黑色素瘤患者，7618 名对照者；美国 1：1804 名黑色素瘤患者，1026 名对照者；美国 2：585 名黑色素瘤患者，6500 名对照者）。所有病例对照研究的合并荟萃分析确定了 1q21.3 上的一个新的易感基因座（rs7412746，P = 9.0×10(-11)，联合复制队列中的 OR 为 0.89（95%CI 0.85-0.95））。我们还表明，黑色素瘤与 1q42.12（rs3219090，P = 9.3×10(-8)）之间存在关联。1q21.3 基因座上的相关变异体跨越了一个包含十个基因的区域，黑色素瘤易感的候选基因包括 ARNT 和 SETDB1。1q21.3 基因座上的变异体似乎与人类色素沉着或痣密度的测量值无关。
