1p36和1q42上的常见变异与皮肤基底细胞癌相关，但与黑色素瘤或色素沉着特征无关。

Common variants on 1p36 and 1q42 are associated with cutaneous basal cell carcinoma but not with melanoma or pigmentation traits.

作者信息

Stacey Simon N, Gudbjartsson Daniel F, Sulem Patrick, Bergthorsson Jon T, Kumar Rajiv, Thorleifsson Gudmar, Sigurdsson Asgeir, Jakobsdottir Margret, Sigurgeirsson Bardur, Benediktsdottir Kristrun R, Thorisdottir Kristin, Ragnarsson Rafn, Scherer Dominique, Rudnai Peter, Gurzau Eugene, Koppova Kvetoslava, Höiom Veronica, Botella-Estrada Rafael, Soriano Virtudes, Juberías Pablo, Grasa Matilde, Carapeto Francisco J, Tabuenca Pilar, Gilaberte Yolanda, Gudmundsson Julius, Thorlacius Steinunn, Helgason Agnar, Thorlacius Theodora, Jonasdottir Aslaug, Blondal Thorarinn, Gudjonsson Sigurjon A, Jonsson Gudbjörn F, Saemundsdottir Jona, Kristjansson Kristleifur, Bjornsdottir Gyda, Sveinsdottir Steinunn G, Mouy Magali, Geller Frank, Nagore Eduardo, Mayordomo José I, Hansson Johan, Rafnar Thorunn, Kong Augustine, Olafsson Jon H, Thorsteinsdottir Unnur, Stefansson Kari

机构信息

deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.

出版信息

Nat Genet. 2008 Nov;40(11):1313-8. doi: 10.1038/ng.234. Epub 2008 Oct 12.

DOI:10.1038/ng.234

PMID:18849993

Abstract

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers.

摘要

为了寻找会增加皮肤基底细胞癌（BCC）风险的新序列变异，我们对930名冰岛基底细胞癌患者和33117名对照者进行了全基因组单核苷酸多态性（SNP）关联研究。在分析了304083个SNP后，我们在1p36和1q42位点观察到信号，并在来自冰岛和东欧的其他样本集中重复了这些关联。总体而言，最显著的信号来自1p36上的rs7538876（比值比[OR]=1.28，P=4.4×10⁻¹²）和1q42上的rs801114（OR=1.28，P=5.9×10⁻¹²）。1p36位点包含候选基因PADI4、PADI6、RCC2和ARHGEF10L，最靠近1q42位点的基因是RAS同源物RHOU。这两个位点均与已知的基底细胞癌风险因素——白皙色素沉着特征无关，且未观察到与黑色素瘤相关的风险。欧洲血统个体中约1.6%的人这两种变异均为纯合子，他们患基底细胞癌的估计风险是非携带者的2.68倍。