Journal article

Genome-wide association study identifies novel loci predisposing to cutaneous melanoma

Christopher I Amos, Li-E Wang, Jeffrey E Lee, Jeffrey E Gershenwald, Wei V Chen, Shenying Fang, Roman Kosoy, Mingfeng Zhang, Abrar A Qureshi, Selina Vattathil, Christopher W Schacherer, Julie M Gardner, Yuling Wang, D Tim Bishop, Jennifer H Barrett, Stuart MacGregor, Nicholas K Hayward, Nicholas G Martin, David L Duffy, Graham J Mann Show all

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2011

Abstract

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is asso..

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Funding Acknowledgements

Research at MD Anderson Cancer Center was partially supported by NIH grants R01CA100264, 2P50CA093459, P30CA016672, R01CA133996 and by the Marit Peterson Fund for Melanoma Research.The Center for Inherited Disease Research is supported by contract HHSN268200782096C. Geneva is supported by NIH grant HG004446.The Australian Twin Registry is supported by an Australian National Health and Medical Research Council (NHMRC) Enabling Grant (2004-2009).The QIMR Study was supported by grants from the Melanoma Research Alliance, the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927,389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498), the Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne), and donations from Neville and Shirley Hawkins.S.M. is supported by NHMRC Career Development Awards (496674, 613705). G. W. M. is supported by the NHMRC Fellowships Scheme.The AMFS study is funded by the National Health and Medical Research Council of Australia (NHMRC) (project grants 566946, 107359, 211172 and program grant number 402761 to G.J.M. and R. F. K.); the Cancer Council New South Wales (project grant 77/00, 06/10), the Cancer Council Victoria and the Cancer Council Queensland (project grant 371); and the US National Institutes of Health (via RO1 grant CA-83115-01A2 to the international Melanoma Genetics Consortium - GenoMEL). A. E. C. is the recipient of an NHMRC public health postdoctoral fellowship (520018) and a National Cancer Institute NSW Early Career Development Fellowship (10/ECF/2-06). B.K.A.'s research is supported by a University of Sydney Medical Foundation Program Grant, and J.L.H. is an Australia Fellow of the NHMRC.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, and Cancer Research UK Project Grant C8216/A6129; and by US National Institutes of Health R01 CA83115. This research was also supported by the Intramural Research Program of the NIH, NCI and DCEG.Emilia-Romagna: National Cancer Institute grants RO1 CA5558 to Maria Teresa Landi.Genoa: IRCSS 2007 Italian Ministry of Health DGRST.4/4235-P1.9.A.B, Fondazione CARIGE, PRIN 2008 to G.B.-S.Leeds: Cancer Research UK Programme grants Genetic Epidemiology of Cancer C588/A10589, C588/A4994 and Cancer Research UK Project grant C8216/A6129.Lund: Swedish Cancer Society, Swedish Research Council, Region Skane funds, Kamprad Foundation.Norway: Grants from the Comprehensive Cancer Center, Oslo University Hospital and the University of Bergen.Paris: Grants from Institut National du Cancer (INCa-PL016) and Ligue Nationale Contre Le Cancer (PRE05/FD and PRE 09/FD) to Florence Demenais, Programme Hospitalier de Recherche Clinique (PHRC 2007/AOM-07-195) to Marie-Francoise Avril and Florence Demenais, Institut National du Cancer (Melanoma Network RS Number 13), Association pour la Recherche sur le Cancer (ARC No. A09/5/5003), and Societe Francaise de Dermatologie (SFD2009) to Brigitte Bressac-de Paillerets. Brigitte Bressac-de Paillerets has been awarded an INSERM Research Fellowship for hospital-based scientists.