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

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 associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
Case-Control Studies
Chromosomes, Human, Pair 1
Genetic Loci
Genetic Markers
Genetic Predisposition to Disease
Genome-Wide Association Study
Guanine Nucleotide Exchange Factors
Humans
Melanoma
Meta-Analysis as Topic
Pigmentation
Polymorphism, Single Nucleotide
Skin Neoplasms

Wang, Li-E (author)
Lee, Jeffrey E (author)
Gershenwald, Jeffrey E (author)
Chen, Wei V (author)
Fang, Shenying (author)
Kosoy, Roman (author)
Zhang, Mingfeng (author)
Qureshi, Abrar A (author)
Vattathil, Selina (author)
Schacherer, Christopher W (author)
Gardner, Julie M (author)
Wang, Yuling (author)
Bishop, D Tim (author)
Barrett, Jennifer H (author)
MacGregor, Stuart (author)
Hayward, Nicholas K (author)
Martin, Nicholas G (author)
Duffy, David L (author)
Mann, Graham J (author)
Cust, Anne (author)
Hopper, John (author)
Brown, Kevin M (author)
Grimm, Elizabeth A (author)
Xu, Yaji (author)
Han, Younghun (author)
Jing, Kaiyan (author)
McHugh, Caitlin (author)
Laurie, Cathy C (author)
Doheny, Kim F (author)
Pugh, Elizabeth W (author)
Seldin, Michael F (author)
Han, Jiali (author)
Wei, Qingyi (author)
Olsson, HåkanLund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumörmikromiljö,Institutionen för kliniska vetenskaper, Lund,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Tumor microenvironment,Department of Clinical Sciences, Lund,Lund Melanoma Study Group,Lund University Research Groups(Swepub:lu)onk-hol (author)
Medicinsk onkologiSektion I (creator_code:org_t)
GenoMEL Investigators

In:Human Molecular Genetics: Oxford University Press (OUP)20:24, s. 23-50120964-69061460-2083

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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