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Genetic variants in ELOVL2 and HSD17B12 predict melanoma-specific survival.

dc.contributor.author Luo, Sheng
dc.contributor.author Wei, Qingyi
dc.contributor.author Dai, Wei
dc.contributor.author Liu, Hongliang
dc.contributor.author Xu, Xinyuan
dc.contributor.author Ge, Jie
dc.contributor.author Zhu, Dakai
dc.contributor.author Amos, Christopher I
dc.contributor.author Fang, Shenying
dc.contributor.author Lee, Jeffrey E
dc.contributor.author Li, Xin
dc.contributor.author Nan, Hongmei
dc.contributor.author Li, Chunying
dc.date.accessioned 2019-03-01T14:28:31Z
dc.date.available 2019-03-01T14:28:31Z
dc.date.issued 2019-02-08
dc.identifier.issn 0020-7136
dc.identifier.issn 1097-0215
dc.identifier.uri https://hdl.handle.net/10161/18098
dc.description.abstract 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.
dc.language eng
dc.publisher Wiley
dc.relation.ispartof International journal of cancer
dc.relation.isversionof 10.1002/ijc.32194
dc.subject cutaneous melanoma
dc.subject fatty acid synthesis
dc.subject genome-wide association study
dc.subject melanoma-specific survival
dc.subject single-nucleotide polymorphism
dc.title Genetic variants in ELOVL2 and HSD17B12 predict melanoma-specific survival.
dc.type Journal article
dc.date.updated 2019-03-01T14:28:31Z
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Population Health Sciences
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
duke.contributor.orcid Luo, Sheng|0000-0003-4214-5809
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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