Genetic Variants in WNT2B and BTRC Predict Melanoma Survival

Abstract

Cutaneous melanoma (CM) is the most lethal skin cancer. The Wnt pathway has an impact on development, invasion and metastasis of CM, thus likely affecting CM prognosis. Using data from a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center, we assessed the associations of 19,830 common single-nucleotide polymorphisms (SNPs) in 151 Wnt pathway autosomal genes with CM-specific survival (CMSS) and then validated significant SNPs in another GWAS from Harvard University. In the single-locus analysis, 1,855 SNPs were significantly associated with CMSS at P < 0.05, of which 547 SNPs were still considered noteworthy after the correction by the false positive report probability. In the replication, two SNPs remained significantly associated with CMSS after multiple comparison correction. By performing functional prediction and stepwise selection, we identified two independent SNPs (i.e., WNT2B rs1175649 G>T and BTRC rs61873997 G>A) that showed a predictive role in CMSS, with an effect-allele-attributed hazards ratio [adjHR of 1.99 (95% confidence interval (CI) = 1.41-2.81, P = 8.10E-05) and 0.61 (0.46-0.80, 3.12E-04), respectively]. Collectively, these variants in the Wnt pathway genes may be biomarkers for outcomes of CM patients, if validated by larger studies.