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

被引：99

作者：

Stacey, Simon N. ^{[1
]}

Gudbjartsson, Daniel F. ^{[1
]}

Sulem, Patrick ^{[1
]}

Bergthorsson, Jon T. ^{[1
]}

Kumar, Rajiv ^{[2
]}

Thorleifsson, Gudmar ^{[1
]}

Sigurdsson, Asgeir ^{[1
]}

Jakobsdottir, Margret ^{[1
]}

Sigurgeirsson, Bardur ^{[3
,4
,15
]}

Benediktsdottir, Kristrun R. ^{[3
,4
,15
]}

Thorisdottir, Kristin ^{[3
,4
,15
]}

Ragnarsson, Rafn ^{[3
,4
,15
]}

Scherer, Dominique ^{[2
]}

Rudnai, Peter ^{[5
]}

Gurzau, Eugene ^{[6
]}

Koppova, Kvetoslava ^{[7
]}

Hoiom, Veronica ^{[8
]}

Botella-Estrada, Rafael ^{[9
]}

Soriano, Virtudes ^{[9
]}

Juberias, Pablo ^{[10
]}

Grasa, Matilde ^{[10
]}

Carapeto, Francisco J. ^{[10
]}

Tabuenca, Pilar ^{[11
]}

Gilaberte, Yolanda ^{[12
]}

Gudmundsson, Julius ^{[1
]}

Thorlacius, Steinunn ^{[1
]}

Helgason, Agnar ^{[1
]}

Thorlacius, Theodora ^{[1
]}

Jonasdottir, Aslaug ^{[1
]}

Blondal, Thorarinn ^{[1
]}

Gudjonsson, Sigurjon A. ^{[1
]}

Jonsson, Gudbjroern F. ^{[1
]}

Saemundsdottir, Jona ^{[1
]}

Kristjansson, Kristleifur ^{[1
]}

Bjornsdottir, Gyda ^{[1
]}

Sveinsdottir, Steinunn G. ^{[13
]}

Mouy, Magali ^{[1
]}

Geller, Frank ^{[1
]}

Nagore, Eduardo ^{[9
]}

Mayordomo, Jose I. ^{[14
]}

Hansson, Johan ^{[8
]}

Rafnar, Thorunn ^{[1
]}

Kong, Augustine ^{[1
]}

Olafsson, Jon H. ^{[3
,4
,15
]}

Thorsteinsdottir, Unnur ^{[1
]}

Stefansson, Kari ^{[1
]}

机构：

[1] Decode Genet, IS-101 Reykjavik, Iceland

[2] German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany

[3] Landspitali Univ Hosp, Dept Dermatol, IS-101 Reykjavik, Iceland

[4] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland

[5] Natl Inst Environm Hlth, H-1450 Budapest, Hungary

[6] Ctr Environm Hlth, Cluj Napoca, Romania

[7] State Hlth Inst, SK-97556 Banska Bystrica, Slovakia

[8] Karolinska Univ Hosp Solna, Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, S-17176 Stockholm, Sweden

[9] Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain

[10] Univ Hosp, Div Dermatol, Zaragoza 50009, Spain

[11] Hlth Sci Inst, Zaragoza 50009, Spain

[12] San Jorge Gen Hosp, Div Dermatol, Huesca 22004, Spain

[13] Clin Res Ctr, IS-110 Reykjavik, Iceland

[14] Univ Hosp, Div Med Oncol, Zaragoza 50009, Spain

[15] Landspitali Univ Hosp, Dept Plast Surg, IS-101 Reykjavik, Iceland

来源：

NATURE GENETICS | 2008年 / 40卷 / 11期

关键词：

D O I：

10.1038/ng.234

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1313 / 1318

页数：6

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