TY - JOUR
T1 - Genome-wide association study identifies three new melanoma susceptibility loci
AU - Barrett, Jennifer H.
AU - Iles, Mark M.
AU - Harland, Mark
AU - Taylor, John C.
AU - Aitken, Joanne F.
AU - Andresen, Per Arne
AU - Akslen, Lars A.
AU - Armstrong, Bruce K.
AU - Avril, Marie Francoise
AU - Azizi, Esther
AU - Bakker, Bert
AU - Bergman, Wilma
AU - Bianchi-Scarrà, Giovanna
AU - Bressac-De Paillerets, Brigitte
AU - Calista, Donato
AU - Cannon-Albright, Lisa A.
AU - Corda, Eve
AU - Cust, Anne E.
AU - Dȩbniak, Tadeusz
AU - Duffy, David
AU - Dunning, Alison M.
AU - Easton, Douglas F.
AU - Friedman, Eitan
AU - Galan, Pilar
AU - Ghiorzo, Paola
AU - Giles, Graham G.
AU - Hansson, Johan
AU - Hocevar, Marko
AU - Höiom, Veronica
AU - Hopper, John L.
AU - Ingvar, Christian
AU - Janssen, Bart
AU - Jenkins, Mark A.
AU - Jönsson, Göran
AU - Kefford, Richard F.
AU - Landi, Giorgio
AU - Landi, Maria Teresa
AU - Lang, Julie
AU - Lubiński, Jan
AU - MacKie, Rona
AU - Malvehy, Josep
AU - Martin, Nicholas G.
AU - Molven, Anders
AU - Montgomery, Grant W.
AU - Van Nieuwpoort, Frans A.
AU - Novakovic, Srdjan
AU - Olsson, Håkan
AU - Pastorino, Lorenza
AU - Puig, Susana
AU - Puig-Butille, Joan Anton
AU - Randerson-Moor, Juliette
AU - Snowden, Helen
AU - Tuominen, Rainer
AU - Van Belle, Patricia
AU - Van Der Stoep, Nienke
AU - Whiteman, David C.
AU - Zelenika, Diana
AU - Han, Jiali
AU - Fang, Shenying
AU - Lee, Jeffrey E.
AU - Wei, Qingyi
AU - Lathrop, G. Mark
AU - Gillanders, Elizabeth M.
AU - Brown, Kevin M.
AU - Goldstein, Alisa M.
AU - Kanetsky, Peter A.
AU - Mann, Graham J.
AU - MacGregor, Stuart
AU - Elder, David E.
AU - Amos, Christopher I.
AU - Hayward, Nicholas K.
AU - Gruis, Nelleke A.
AU - Demenais, Florence
AU - Bishop, Julia A.Newton
AU - Bishop, D. Timothy
N1 - Funding Information:
Leeds: Cancer Research UK Programme grants for Genetic epidemiology of cancer (C588/A10589 and C588/A4994) and Cancer Research UK Project grant (C8216/A6129) and Leeds Cancer Research UK Centre (C37059/A11941).
Funding Information:
Stockholm: Grants were provided by the Swedish Cancer Society (100279), the Swedish Research Council (K2006-74X-20141-01-3), Radiumhemmet Research Funds (101152) and Karolinska Institutet Research Funds (2010Fobi0450).
Funding Information:
Cambridge: D.F.E. is a Principal Research Fellow of Cancer Research UK. SEARCH is funded by grants from Cancer Research UK (C8197/A10123, C8197/A10123 and C490/A10124). A.M.D. has been supported by a Cancer Research UK grant (C8197/A10865) and by the Joseph Mitchell Fund.
Funding Information:
The authors are extremely grateful for the contributions of D. Seminara to the work of GenoMEL and also for the support of G. Cross (University of Leeds) for maintaining the study wiki. Overall, the GenoMEL Consortium is indebted to the organizational skills of P. Affleck. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from their website (see URLs). Funding for the project was provided by the Wellcome Trust under award 076113.
Funding Information:
The authors thank the Epidemiological Study on the Genetics and Environment of Asthma (EGEA) cooperative group for giving access to data of the EGEA study. We acknowledge that the biological specimens of the French Familial Melanoma Study Group were obtained from the Institut Gustave Roussy and Fondation Jean Dausset–CEPH Biobanks. The GenoMEL study was funded by the European Commission under the 6th Framework Programme (contract no. LSHC-CT-2006-018702), by Cancer Research UK Programme Awards (C588/A4994 and C588/A10589), by a Cancer Research UK Project grant (C8216/A6129) and by a grant from the US National Institutes of Health (NIH; CA83115). This research was also supported by the Intramural Research Program of the NIH, National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics. Funding specific to particular locations is acknowledged below.
Funding Information:
Lund: Funding by the Swedish Cancer Society, Swedish Research Council, Region Skåne funds, Kamprad Foundation.
Funding Information:
Australia: Melanoma Research Alliance, US NCI (CA088363, CA083115, CA122838, CA87969, CA055075, CA100264, CA133996 and CA49449), the National Health and Medical Research Council of Australia (NHMRC) (107359, 200071, 241944, 339462, 380385, 389927, 389875, 389891, 389892, 389938, 402761, 443036, 442915, 442981, 496610, 496675, 520018, 496739, 552485 and 552498), the Cancer Councils NSW, Victoria and Queensland, the Cancer Institute New South Wales, the Cooperative Research Centre (CRC) for Discovery of Genes for Common Human Diseases, Cerylid Biosciences (Melbourne) and the Australian Cancer Research Foundation.
Funding Information:
Paris: Grants from Institut National du Cancer (INCa-PL016) and Ligue Nationale Contre Le Cancer (PRE05/FD and PRE 09/FD) to F. Demenais, Programme Hospitalier de Recherche Clinique (AOM-07-195) to M.-F. Avril and F. Demenais, Institut National du Cancer (Melanoma Network RS 13), Association pour la Recherche sur le Cancer (ARC A09/5/5003) and Société Française de Dermatologie (SFD2009) to B.B.-deP. B.B.-deP. has been awarded an INSERM Research Fellowship for hospital-based scientists.
PY - 2011/11
Y1 - 2011/11
N2 - 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 × 10 -9), an SNP in MX2 (rs45430, P = 2.9 × 10 -9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10 -10). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10 -7 under a fixed-effects model and P = 1.2 × 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.
AB - 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 × 10 -9), an SNP in MX2 (rs45430, P = 2.9 × 10 -9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10 -10). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10 -7 under a fixed-effects model and P = 1.2 × 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.
UR - http://www.scopus.com/inward/record.url?scp=80054996042&partnerID=8YFLogxK
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U2 - 10.1038/ng.959
DO - 10.1038/ng.959
M3 - Article
C2 - 21983787
AN - SCOPUS:80054996042
SN - 1061-4036
VL - 43
SP - 1108
EP - 1113
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -