Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival.
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Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings.
Proportional Hazards Models
Polymorphism, Single Nucleotide
Aged, 80 and over
Fanconi Anemia Complementation Group A Protein
Published Version (Please cite this version)10.1038/jid.2014.416
Publication InfoYin, Jieyun; Liu, Hongliang; Liu, Zhensheng; Wang, Li-E; Chen, Wei V; Zhu, Dakai; ... Wei, Qingyi (2015). Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival. The Journal of investigative dermatology, 135(2). pp. 542-550. 10.1038/jid.2014.416. Retrieved from https://hdl.handle.net/10161/18033.
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Assistant Professor of Medicine
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
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