TY - JOUR
T1 - Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival
AU - Yin, Jieyun
AU - Liu, Hongliang
AU - Liu, Zhensheng
AU - Wang, Li E.
AU - Chen, Wei V.
AU - Zhu, Dakai
AU - Amos, Christopher I.
AU - Fang, Shenying
AU - Lee, Jeffrey E.
AU - Wei, Qingyi
N1 - Publisher Copyright:
© 2015 The Society for Investigative Dermatology.
PY - 2015/2/13
Y1 - 2015/2/13
N2 - 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 melanomaspecific 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.
AB - 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 melanomaspecific 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.
UR - http://www.scopus.com/inward/record.url?scp=84929504750&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929504750&partnerID=8YFLogxK
U2 - 10.1038/jid.2014.416
DO - 10.1038/jid.2014.416
M3 - Article
C2 - 25243787
AN - SCOPUS:84929504750
SN - 0022-202X
VL - 135
SP - 542
EP - 550
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -