Genome-wide association study identifies three new melanoma susceptibility loci

被引：200

作者：

Barrett, Jennifer H. ^{[1
]}

Iles, Mark M. ^{[1
]}

Harland, Mark ^{[1
]}

Taylor, John C. ^{[1
]}

Aitken, Joanne F. ^{[2
]}

Andresen, Per Arne ^{[3
]}

Akslen, Lars A. ^{[4
,5
]}

Armstrong, Bruce K. ^{[6
]}

Avril, Marie-Francoise ^{[7
]}

Azizi, Esther ^{[8
,9
,10
]}

Bakker, Bert ^{[11
]}

Bergman, Wilma ^{[12
]}

Bianchi-Scarra, Giovanna ^{[13
]}

Bressac-de Paillerets, Brigitte ^{[14
,15
]}

Calista, Donato ^{[16
]}

Cannon-Albright, Lisa A. ^{[17
]}

Corda, Eve ^{[14
]}

Cust, Anne E. ^{[18
,19
]}

Debniak, Tadeusz ^{[20
]}

Duffy, David ^{[21
]}

Dunning, Alison M. ^{[22
]}

Easton, Douglas F. ^{[22
,23
]}

Friedman, Eitan ^{[8
,9
,10
]}

Galan, Pilar ^{[24
,25
]}

Ghiorzo, Paola ^{[13
]}

Giles, Graham G. ^{[18
,26
]}

Hansson, Johan ^{[27
]}

Hocevar, Marko ^{[28
]}

Hoeiom, Veronica ^{[27
]}

Hopper, John L. ^{[18
]}

Ingvar, Christian ^{[29
]}

Janssen, Bart ^{[30
]}

Jenkins, Mark A. ^{[18
]}

Joensson, Goeran ^{[31
]}

Kefford, Richard F. ^{[6
]}

Landi, Giorgio ^{[16
]}

Landi, Maria Teresa ^{[32
]}

Lang, Julie ^{[33
]}

Lubinski, Jan ^{[20
]}

Mackie, Rona ^{[33
]}

Malvehy, Josep ^{[34
]}

Martin, Nicholas G. ^{[21
]}

Molven, Anders ^{[4
,5
]}

Montgomery, Grant W. ^{[21
]}

van Nieuwpoort, Frans A. ^{[12
]}

Novakovic, Srdjan ^{[28
]}

Olsson, Hakan ^{[31
]}

Pastorino, Lorenza ^{[13
]}

Puig, Susana ^{[34
,35
]}

Puig-Butille, Joan Anton ^{[34
,35
]}

机构：

[1] St James Univ Hosp, Leeds Canc Res UK Ctr, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England

[2] Canc Council, Viertel Ctr Res Canc Control, Brisbane, Qld, Australia

[3] Oslo Univ Hosp, Rikshosp, Dept Pathol, Oslo, Norway

[4] Univ Bergen, Gade Inst, Bergen, Norway

[5] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway

[6] Westmead Millennium Inst, Westmead, NSW, Australia

[7] Univ Descartes, Serv Dermatol, Hop Cochin, Assistance Publ Hop Paris, Paris, France

[8] Sheba Med Ctr, Dept Dermatol, Tel Hashomer, Israel

[9] Sheba Med Ctr, Oncogenet Unit, Tel Hashomer, Israel

[10] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel

[11] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Dept Clin Genet, Leiden, Netherlands

[12] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands

[13] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy

[14] Fdn Jean Daussel CEPH, INSERM, U946, Paris, France

[15] Inst Canc Gustave Roussy, Serv Genet, Dept Biopathol, Villejuif, France

[16] Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy

[17] Univ Utah, Sch Med, Dept Internal Med, Div Genet Epidemiol, Salt Lake City, UT USA

[18] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[19] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia

[20] Pomeranian Med Univ, Int Hereditary Canc Ctr, Szczecin, Poland

[21] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[22] Univ Cambridge, Dept Oncol, Cambridge, England

[23] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[24] INSERM, UMR U557, Bobigny, France

[25] Ctr Rech Nutr Humaine, Inst Natl Rech Agron, U1125, Bobigny, France

[26] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[27] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden

[28] Inst Oncol Ljubljana, Ljubljana, Slovenia

[29] Univ Lund Hosp, Dept Surg, S-22185 Lund, Sweden

[30] ServiceXS, Leiden, Netherlands

[31] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden

[32] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[33] Univ Glasgow, Dept Med Genet, Glasgow, Lanark, Scotland

[34] Univ Barcelona, Inst Invest Biomed August Pi Sune, Dept Dermatol, Melanoma Unit,Hosp Clin, Barcelona, Spain

[35] Inst Salud Carlos III, Ctr Biomed Res Rare Dis CIBERER, Barcelona, Spain

[36] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[37] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, Evry, France

[38] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA

[39] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA

[40] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[41] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Unit 1365, Houston, TX 77030 USA

[42] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[43] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA

[44] NCI, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD USA

[45] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

[46] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[47] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA

[48] Univ Paris 07, Inst Univ Hematol, Paris, France

来源：

NATURE GENETICS | 2011年 / 43卷 / 11期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

CUTANEOUS MELANOMA; PHENOTYPIC CHARACTERISTICS; MALIGNANT-MELANOMA; SEQUENCE VARIANTS; RISK; CANCER; WOMEN; GENE; METAANALYSIS; EXPOSURE;

D O I：

10.1038/ng.959

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.

引用

页码：1108 / U98

页数：7

共 35 条

[1]

[Anonymous], 2006, QUANTO 1.1 A Computer Program for Power and Sample Size Calculations for Genetic-Epidemiology Studies

[2] Variation at the TERT locus and predisposition for cancer [J].

Baird, Duncan M. .

EXPERT REVIEWS IN MOLECULAR MEDICINE, 2010, 12

[3] Risk of cutaneous melanoma in relation to the numbers, types and sites of naevi: A case-control study [J].

Bataille, V ;

Bishop, JAN ;

Sasieni, P ;

Swerdlow, AJ ;

Pinney, E ;

Griffiths, K ;

Cuzickz, J .

BRITISH JOURNAL OF CANCER, 1996, 73 (12) :1605-1611

[4] Genome-wide association study identifies three loci associated with melanoma risk [J].

Bishop, D. Timothy ;

Demenais, Florence ;

Iles, Mark M. ;

Harland, Mark ;

Taylor, John C. ;

Corda, Eve ;

Randerson-Moor, Juliette ;

Aitken, Joanne F. ;

Avril, Marie-Francoise ;

Azizi, Esther ;

Bakker, Bert ;

Bianchi-Scarra, Giovanna ;

Bressac-de Paillerets, Brigitte ;

Calista, Donato ;

Cannon-Albright, Lisa A. ;

Chin-A-Woeng, Thomas ;

Debniak, Tadeusz ;

Galore-Haskel, Gilli ;

Ghiorzo, Paola ;

Gut, Ivo ;

Hansson, Johan ;

Hocevar, Marko ;

Hoiom, Veronica ;

Hopper, John L. ;

Ingvar, Christian ;

Kanetsky, Peter A. ;

Kefford, Richard F. ;

Landi, Maria Teresa ;

Lang, Julie ;

Lubinski, Jan ;

Mackie, Rona ;

Malvehy, Josep ;

Mann, Graham J. ;

Martin, Nicholas G. ;

Montgomery, Grant W. ;

van Nieuwpoort, Frans A. ;

Novakovic, Srdjan ;

Olsson, Hakan ;

Puig, Susana ;

Weiss, Marjan ;

van Workum, Wilbert ;

Zelenika, Diana ;

Brown, Kevin M. ;

Goldstein, Alisa M. ;

Gillanders, Elizabeth M. ;

Boland, Anne ;

Galan, Pilar ;

Elder, David E. ;

Gruis, Nelleke A. ;

Hayward, Nicholas K. .

NATURE GENETICS, 2009, 41 (08) :920-U85

[5] Common sequence variants on 20q11.22 confer melanoma susceptibility [J].

Brown, Kevin M. ;

MacGregor, Stuart ;

Montgomery, Grant W. ;

Craig, David W. ;

Zhao, Zhen Zhen ;

Iyadurai, Kelly ;

Henders, Anjali K. ;

Homer, Nils ;

Campbell, Megan J. ;

Stark, Mitchell ;

Thomas, Shane ;

Schmid, Helen ;

Holland, Elizabeth A. ;

Gillanders, Elizabeth M. ;

Duffy, David L. ;

Maskiell, Judith A. ;

Jetann, Jodie ;

Ferguson, Megan ;

Stephan, Dietrich A. ;

Cust, Anne E. ;

Whiteman, David ;

Green, Adele ;

Olsson, Hakan ;

Puig, Susana ;

Ghiorzo, Paola ;

Hansson, Johan ;

Demenais, Florence ;

Goldstein, Alisa M. ;

Gruis, Nelleke A. ;

Elder, David E. ;

Bishop, Julia Newton ;

Kefford, Richard F. ;

Giles, Graham G. ;

Armstrong, Bruce K. ;

Aitken, Joanne F. ;

Hopper, John L. ;

Martin, Nicholas G. ;

Trent, Jeffrey M. ;

Mann, Graham J. ;

Hayward, Nicholas K. .

NATURE GENETICS, 2008, 40 (07) :838-840

[6]

Cannon-Albright L A, 1991, Important Adv Oncol, P39

[7] A pooled analysis of Melanocytic nevus phenotype and the risk of cutaneous melanoma at different latitudes [J].

Chang, Yu-mei ;

Newton-Bishop, Julia A. ;

Bishop, D. Timothy ;

Armstrong, Bruce K. ;

Bataille, Veronique ;

Bergman, Wilma ;

Berwick, Marianne ;

Bracci, Paige M. ;

Elwood, J. Mark ;

Ernstoff, Marc S. ;

Green, Adele C. ;

Gruis, Nelleke A. ;

Holly, Elizabeth A. ;

Ingvar, Christian ;

Kanetsky, Peter A. ;

Karagas, Margaret R. ;

Le Marchand, Loic ;

Mackie, Rona M. ;

Olsson, Hakan ;

Osterlind, Anne ;

Rebbeck, Timothy R. ;

Reich, Kristian ;

Sasieni, Peter ;

Siskind, Victor ;

Swerdlow, Anthony J. ;

Titus-Ernstoff, Linda ;

Zens, Michael S. ;

Ziegler, Andreas ;

Barrett, Jennifer H. .

INTERNATIONAL JOURNAL OF CANCER, 2009, 124 (02) :420-428

[8] Testing for association on the X chromosome [J].

Clayton, David .

BIOSTATISTICS, 2008, 9 (04) :593-600

[9] Distinct sets of genetic alterations in melanoma [J].

Curtin, JA ;

Fridlyand, J ;

Kageshita, T ;

Patel, HN ;

Busam, KJ ;

Kutzner, H ;

Cho, KH ;

Aiba, S ;

Bröcker, EB ;

LeBoit, PE ;

Pinkel, D ;

Bastian, BC .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (20) :2135-2147

[10] METAANALYSIS IN CLINICAL-TRIALS [J].

DERSIMONIAN, R ;

LAIRD, N .

CONTROLLED CLINICAL TRIALS, 1986, 7 (03) :177-188

← 1 2 3 4 →