ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma

被引：256

作者：

Gudbjartsson, Daniel F. ^{[1
]}

Sulem, Patrick ^{[1
]}

Stacey, Simon N. ^{[1
]}

Goldstein, Alisa M. ^{[2
]}

Rafnar, Thorunn ^{[1
]}

Sigurgeirsson, Bardur ^{[3
,4
]}

Benediktsdottir, Kristrun R. ^{[3
,4
,5
]}

Thorisdottir, Kristin ^{[3
,4
,5
]}

Ragnarsson, Rafn

Sveinsdottir, Steinunn G. ^{[6
]}

Magnusson, Veronica ^{[7
]}

Lindblom, Annika ^{[8
]}

Kostulas, Konstantinos ^{[9
]}

Botella-Estrada, Rafael ^{[10
]}

Soriano, Virtudes ^{[11
]}

Juberias, Pablo ^{[12
]}

Grasa, Matilde ^{[12
]}

Saez, Berta ^{[13
]}

Andres, Raquel ^{[14
]}

Scherer, Dominique ^{[15
]}

Rudnai, Peter ^{[16
]}

Gurzau, Eugene ^{[17
]}

Koppova, Kvetoslava ^{[18
]}

Kiemeney, Lambertus A. ^{[19
,20
,21
]}

Jakobsdottir, Margret ^{[1
]}

Steinberg, Stacy ^{[1
]}

Helgason, Agnar ^{[1
]}

Gretarsdottir, Solveig ^{[1
]}

Tucker, Margaret A. ^{[2
]}

Mayordomo, Jose I. ^{[14
]}

Nagore, Eduardo ^{[11
]}

Kumar, Rajiv ^{[15
]}

Hansson, Johan

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

Gulcher, Jeffrey ^{[1
]}

Kong, Augustine ^{[1
]}

Thorsteinsdottir, Unnur ^{[1
]}

Stefansson, Kari ^{[1
]}

机构：

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

[2] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Services, Bethesda, MD 20892 USA

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

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

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

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

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

[8] Karolinska Inst, Dept Mol Med, S-17176 Stockholm, Sweden

[9] Karolinska Univ Hosp, Karolinska Inst, Dept Neurol, S-14186 Huddinge, Sweden

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

[11] Inst Valenciano Oncol, Dept Oncol, Valencia 46009, Spain

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

[13] Hlth Sci Inst, Zaragoza 50009, Spain

[14] Hlth Sci Inst, Div Med Oncol, Zaragoza 50009, Spain

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

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

[17] Ctr Environm Hlth, RO Cluj Napoca, Romania

[18] State Hlth Inst, SK-97576 Banska Bystr, Slovakia

[19] Ctr Comprehens Canc, NL-6501 BG Nijmegen, Netherlands

[20] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands

[21] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands

来源：

NATURE GENETICS | 2008年 / 40卷 / 07期

关键词：

D O I：

10.1038/ng.161

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) 1.45, P = 1.2 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 10(-6)). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.

引用

页码：886 / 891

页数：6

共 30 条

[1] Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair [J].

Bastiaens, MT ;

ter Huurne, JAC ;

Kielich, C ;

Gruis, NA ;

Westendorp, RGJ ;

Vermeer, BJ ;

Bavinck, NJB .

AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 68 (04) :884-894

[2] Melanocortin-1 receptor genotype is a risk factor for basal and squamous cell carcinoma [J].

Box, NF ;

Duffy, DL ;

Irving, RE ;

Russell, A ;

Chen, W ;

Griffiths, LR ;

Parsons, PG ;

Green, AC ;

Sturm, RA .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2001, 116 (02) :224-229

[3] A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation [J].

Duffy, David L. ;

Montgomery, Grant W. ;

Chen, Wei ;

Zhao, Zhen Zhen ;

Le, Lien ;

James, Michael R. ;

Hayward, Nicholas K. ;

Martin, Nicholas G. ;

Sturm, Richard A. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (02) :241-252

[4]

Frudakis T, 2003, GENETICS, V165, P2071

[5] Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes [J].

Grant, SFA ;

Thorleifsson, G ;

Reynisdottir, I ;

Benediktsson, R ;

Manolescu, A ;

Sainz, J ;

Helgason, A ;

Stefansson, H ;

Emilsson, V ;

Helgadottir, A ;

Styrkarsdottir, U ;

Magnusson, KP ;

Walters, GB ;

Palsdottir, E ;

Jonsdottir, T ;

Gudmundsdottir, T ;

Gylfason, A ;

Saemundsdottir, J ;

Wilensky, RL ;

Reilly, MP ;

Rader, DJ ;

Bagger, Y ;

Christiansen, C ;

Gudnason, V ;

Sigurdsson, G ;

Thorsteinsdottir, U ;

Gulcher, JR ;

Kong, A ;

Stefansson, K .

NATURE GENETICS, 2006, 38 (03) :320-323

[6] The gene encoding phosphodiesterase 4D confers risk of ischemic stroke [J].

Gretarsdottir, S ;

Thorleifsson, G ;

Reynisdottir, ST ;

Manolescu, A ;

Jonsdottir, S ;

Jonsdottir, T ;

Gudmundsdottir, T ;

Bjarnadottir, SM ;

Einarsson, OB ;

Gudjonsdottir, HM ;

Hawkins, M ;

Gudmundsson, G ;

Gudmundsdottir, H ;

Andrason, H ;

Gudmundsdottir, AS ;

Sigurdardottir, M ;

Chou, TT ;

Nahmias, J ;

Goss, S ;

Sveinbjörnsdottir, S ;

Valdimarsson, EM ;

Jakobsson, F ;

Agnarsson, U ;

Gudnason, V ;

Thorgeirsson, G ;

Fingerle, J ;

Gurney, M ;

Gudbjartsson, D ;

Frigge, ML ;

Kong, A ;

Stefansson, K ;

Gulcher, JR .

NATURE GENETICS, 2003, 35 (02) :131-138

[7] Risk factors for skin cancers: a nested case-control study within the Nurses' Health Study [J].

Han, Jiali ;

Colditz, Graham A. ;

Hunter, David J. .

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2006, 35 (06) :1514-1521

[8] Melanocortin 1 receptor variants and skin cancer risk [J].

Han, Jiali ;

Kraft, Peter ;

Colditz, Graham A. ;

Wong, Jason ;

Hunter, David J. .

INTERNATIONAL JOURNAL OF CANCER, 2006, 119 (08) :1976-1984

[9] Cancer statistics, 2007 [J].

Jemal, Ahmedin ;

Siegel, Rebecca ;

Ward, Elizabeth ;

Murray, Taylor ;

Xu, Jiaquan ;

Thun, Michael J. .

CA-A CANCER JOURNAL FOR CLINICIANS, 2007, 57 (01) :43-66

[10] A polymorphism in the agouti signaling protein gene is associated with human pigmentation [J].

Kanetsky, PA ;

Swoyer, J ;

Panossian, S ;

Holmes, R ;

Guerry, D ;

Rebbeck, TR .

AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (03) :770-775

← 1 2 3 →