Joint effect of multiple common SNPs predicts melanoma susceptibility.

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Date

2013-01

Authors

Fang, Shenying
Han, Jiali
Zhang, Mingfeng
Wang, Li-e
Wei, Qingyi
Amos, Christopher I
Lee, Jeffrey E

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Abstract

Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS) comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07). The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69). PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors.

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Humans, Melanoma, Genetic Predisposition to Disease, Computational Biology, Phenotype, Polymorphism, Single Nucleotide, Middle Aged, Female, Male

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0085642

Publication Info

Fang, Shenying, Jiali Han, Mingfeng Zhang, Li-e Wang, Qingyi Wei, Christopher I Amos and Jeffrey E Lee (2013). Joint effect of multiple common SNPs predicts melanoma susceptibility. PloS one, 8(12). p. e85642. 10.1371/journal.pone.0085642 Retrieved from https://hdl.handle.net/10161/17998.

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Scholars@Duke

Wei

Qingyi Wei

Professor in Population Health Sciences

Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and variations in cell death. He is Editor-in-Chief of the open access journal "Cancer Medicine" and Associate Editor-in-Chief of the International Journal of Molecular Epidemiology and Genetics.

Area of Expertise: Epidemiology


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