TY - JOUR
T1 - Genetic variants in ELOVL2 and HSD17B12 predict melanoma-specific survival
AU - Dai, Wei
AU - Liu, Hongliang
AU - Xu, Xinyuan
AU - Ge, Jie
AU - Luo, Sheng
AU - Zhu, Dakai
AU - Amos, Christopher I.
AU - Fang, Shenying
AU - Lee, Jeffrey E.
AU - Li, Xin
AU - Nan, Hongmei
AU - Li, Chunying
AU - Wei, Qingyi
N1 - Publisher Copyright:
© 2019 UICC
PY - 2019/11/15
Y1 - 2019/11/15
N2 - Fatty acids play a key role in cellular bioenergetics, membrane biosynthesis and intracellular signaling processes and thus may be involved in cancer development and progression. In the present study, we comprehensively assessed associations of 14,522 common single-nucleotide polymorphisms (SNPs) in 149 genes of the fatty-acid synthesis pathway with cutaneous melanoma disease-specific survival (CMSS). The dataset of 858 cutaneous melanoma (CM) patients from a published genome-wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used as the discovery dataset, and the identified significant SNPs were validated by a dataset of 409 CM patients from another GWAS from the Nurses’ Health and Health Professionals Follow-up Studies. We found 40 noteworthy SNPs to be associated with CMSS in both discovery and validation datasets after multiple comparison correction by the false positive report probability method, because more than 85% of the SNPs were imputed. By performing functional prediction, linkage disequilibrium analysis, and stepwise Cox regression selection, we identified two independent SNPs of ELOVL2 rs3734398 T>C and HSD17B12 rs11037684 A>G that predicted CMSS, with an allelic hazards ratio of 0.66 (95% confidence interval = 0.51–0.84 and p = 8.34 × 10−4) and 2.29 (1.55–3.39 and p = 3.61 × 10−5), respectively. Finally, the ELOVL2 rs3734398 variant CC genotype was found to be associated with a significantly increased mRNA expression level. These SNPs may be potential markers for CM prognosis, if validated by additional larger and mechanistic studies.
AB - Fatty acids play a key role in cellular bioenergetics, membrane biosynthesis and intracellular signaling processes and thus may be involved in cancer development and progression. In the present study, we comprehensively assessed associations of 14,522 common single-nucleotide polymorphisms (SNPs) in 149 genes of the fatty-acid synthesis pathway with cutaneous melanoma disease-specific survival (CMSS). The dataset of 858 cutaneous melanoma (CM) patients from a published genome-wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used as the discovery dataset, and the identified significant SNPs were validated by a dataset of 409 CM patients from another GWAS from the Nurses’ Health and Health Professionals Follow-up Studies. We found 40 noteworthy SNPs to be associated with CMSS in both discovery and validation datasets after multiple comparison correction by the false positive report probability method, because more than 85% of the SNPs were imputed. By performing functional prediction, linkage disequilibrium analysis, and stepwise Cox regression selection, we identified two independent SNPs of ELOVL2 rs3734398 T>C and HSD17B12 rs11037684 A>G that predicted CMSS, with an allelic hazards ratio of 0.66 (95% confidence interval = 0.51–0.84 and p = 8.34 × 10−4) and 2.29 (1.55–3.39 and p = 3.61 × 10−5), respectively. Finally, the ELOVL2 rs3734398 variant CC genotype was found to be associated with a significantly increased mRNA expression level. These SNPs may be potential markers for CM prognosis, if validated by additional larger and mechanistic studies.
KW - cutaneous melanoma
KW - fatty acid synthesis
KW - genome-wide association study
KW - melanoma-specific survival
KW - single-nucleotide polymorphism
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U2 - 10.1002/ijc.32194
DO - 10.1002/ijc.32194
M3 - Article
C2 - 30734280
AN - SCOPUS:85061932949
SN - 0020-7136
VL - 145
SP - 2619
EP - 2628
JO - International journal of cancer
JF - International journal of cancer
IS - 10
ER -