Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma-specific survival.
Abstract
A few single-nucleotide polymorphisms (SNPs) have been identified to be associated
with cutaneous melanoma (CM) survival through genome-wide association studies, but
stringent multiple testing corrections required for the hypothesis-free testing may
have masked some true associations. Using a hypothesis-driven analysis approach, we
sought to evaluate associations between SNPs in ketone body metabolic pathway genes
and CM survival. We comprehensively assessed associations between 4196 (538 genotyped
and 3658 imputed) common SNPs in 44 ketone body metabolic pathway genes and CM survival,
using a dataset of 858 patients of a case-control study from The University of Texas
M.D. Anderson Cancer Center as the discovery set and another dataset of 409 patients
from the Nurses' Health Study and the Health Professionals Follow-up Study as the
replication set. There were 95/858 (11.1%) and 48/409 (11.7%) patients who died of
CM, respectively. We identified two independent SNPs (ie, PDSS1 rs12254548 G>C and
SLC16A6 rs71387392 G>A) that were associated with CM survival, with allelic hazards
ratios of 0.58 (95% confidence interval [CI] = 0.44-0.76, P = 9.00 × 10-5 ) and 1.98
(95% CI = 1.34-2.94, P = 6.30 × 10-4 ), respectively. Additionally, associations between
genotypes of the SNPs and messenger RNA expression levels of their corresponding genes
support the biologic plausibility of a role for these two variants in CM tumor progression
and survival. Once validated by other larger studies, PDSS1 rs12254548 and SLC16A6
rs71387392 may be valuable biomarkers for CM survival.
Type
Journal articleSubject
cutaneous melanomacutaneous melanoma-specific survival
genome-wide association study
ketone body metabolism
single-nucleotide polymorphism
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https://hdl.handle.net/10161/20711Published Version (Please cite this version)
10.1002/mc.23191Publication Info
Dai, Wei; Liu, Hongliang; Chen, Ka; Xu, Xinyuan; Qian, Danwen; Luo, Sheng; ... Wei,
Qingyi (2020). Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict
cutaneous melanoma-specific survival. Molecular carcinogenesis, 59(6). pp. 640-650. 10.1002/mc.23191. Retrieved from https://hdl.handle.net/10161/20711.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Sheng Luo
Professor of Biostatistics & Bioinformatics

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