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 from The University of Texas MD 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 and then validated significant SNPs in another genome-wide association study from Harvard University. In the single-locus analysis, 1,855 SNPs were significantly associated with CM-specific survival 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 CM-specific survival 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 CM-specific survival, with an effect-allele-attributed hazards ratio (adjusted hazards ratio) of 1.99 (95% confidence interval = 1.41-2.81, P = 8.10 × 10-5) and 0.61 (0.46-0.80, 3.12×10-4), respectively. Collectively, these variants in the Wnt pathway genes may be biomarkers for outcomes of patients with CM, if validated by larger studies.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.