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

被引：164

作者：

Amos, Christopher I. ^{[1
]}

Wang, Li-E

Lee, Jeffrey E. ^{[2
]}

Gershenwald, Jeffrey E. ^{[2
]}

Chen, Wei V.

Fang, Shenying

Kosoy, Roman ^{[4
]}

Zhang, Mingfeng ^{[5
]}

Qureshi, Abrar A. ^{[5
,6
]}

Vattathil, Selina

Schacherer, Christopher W. ^{[2
]}

Gardner, Julie M. ^{[2
]}

Wang, Yuling ^{[2
]}

Bishop, D. Tim ^{[7
]}

Barrett, Jennifer H. ^{[7
]}

MacGregor, Stuart ^{[8
]}

Hayward, Nicholas K. ^{[8
]}

Martin, Nicholas G. ^{[8
]}

Duffy, David L. ^{[8
]}

Mann, Graham J. ^{[9
,10
]}

Cust, Anne ^{[11
]}

Hopper, John ^{[12
]}

Brown, Kevin M. ^{[13
]}

Grimm, Elizabeth A. ^{[3
]}

Xu, Yaji

Han, Younghun

Jing, Kaiyan

McHugh, Caitlin ^{[14
]}

Laurie, Cathy C. ^{[14
]}

Doheny, Kim F. ^{[15
]}

Pugh, Elizabeth W. ^{[15
]}

Seldin, Michael F. ^{[4
]}

Han, Jiali ^{[5
,6
,16
]}

Wei, Qingyi

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Unit 1340, Houston, TX 77030 USA

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

[3] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA

[4] Univ Calif Davis, Rowe Program Genet, Davis, CA 95616 USA

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

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

[7] Univ Leeds, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England

[8] Queensland Inst Med Res, Brisbane, Qld 4029, Australia

[9] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia

[10] Melanoma Inst Australia, Westmead, NSW 2145, Australia

[11] Univ Sydney, Sydney Sch Publ Hlth, CESR, Sydney, NSW 2006, Australia

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

[13] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[14] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[15] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA

[16] Harvard Univ, Channing Lab, Dept Epidemiol, Boston, MA 02115 USA

来源：

HUMAN MOLECULAR GENETICS | 2011年 / 20卷 / 24期

基金：

澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院; 英国医学研究理事会; 瑞典研究理事会;

关键词：

POPULATION; GENE; PIGMENTATION; RISK; VARIANTS; EYE;

D O I：

10.1093/hmg/ddr415

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.

引用

页码：5012 / 5023

页数：12

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