TY - JOUR
T1 - Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma-specific survival
AU - Dai, Wei
AU - Liu, Hongliang
AU - Chen, Ka
AU - Xu, Xinyuan
AU - Qian, Danwen
AU - Luo, Sheng
AU - Amos, Christopher I.
AU - Lee, Jeffrey E.
AU - Li, Xin
AU - Nan, Hongmei
AU - Li, Chunying
AU - Wei, Qingyi
N1 - Publisher Copyright:
© 2020 Wiley Periodicals, Inc.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - cutaneous melanoma
KW - cutaneous melanoma-specific survival
KW - genome-wide association study
KW - ketone body metabolism
KW - single-nucleotide polymorphism
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U2 - 10.1002/mc.23191
DO - 10.1002/mc.23191
M3 - Article
C2 - 32232919
AN - SCOPUS:85082538793
SN - 0899-1987
VL - 59
SP - 640
EP - 650
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 6
ER -