title: Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival.
abstract: 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.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.|Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jieyun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.affiliation: Department of Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, USA.
authors.forename: Wei V
authors.initials: WV
authors.lastname: Chen
authors.affiliation: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, 03755, USA.
authors.forename: Dakai
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, 03755, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
authors.forename: Shenying
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019295:Computational Biology; D005199:Fanconi Anemia / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics*; D005260:Female; D024522:Genes, BRCA2; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012372:ROC Curve; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality
chemical_list: C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein