{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T13:38:26Z","timestamp":1769002706565,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glutamine dependence is a unique metabolic defect seen in cutaneous melanoma (CM), directly influencing the treatment and prognosis. Here, we investigated the associations between 6025 common single\u2010nucleotide polymorphisms (SNPs) in 77 glutamine metabolic pathway genes with CM\u2010specific survival (CMSS) using genotyping datasets from two published genome\u2010wide association studies (GWASs). In the single\u2010locus analysis, 76 SNPs were found to be significantly associated with CMSS (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.050, false\u2010positive report probability\u2009&lt;\u20090.2 and Bayesian false discovery probability\u2009&lt;\u20090.8) in the discovery dataset, of which seven SNPs were replicated in the validation dataset and three SNPs (<jats:italic>HAL<\/jats:italic> rs17676826T\u2009&gt;\u2009C, <jats:italic>LGSN<\/jats:italic> rs12663017T\u2009&gt;\u2009A, and <jats:italic>NOXRED1<\/jats:italic> rs8012548A\u2009&gt;\u2009G) independently predicted CMSS, with an effect\u2010allele attributed adjusted hazards ratio of 1.52 (95% confidence interval\u2009=\u20091.19\u20101.93) and <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001, 0.68 (0.54\u20100.87) and <jats:italic>P<\/jats:italic>\u2009=\u2009.002 and 0.62 (0.46\u20100.83) and <jats:italic>P<\/jats:italic>\u2009=\u2009.002, respectively. The model including the number of unfavorable genotypes (NUGs) of these three SNPs and covariates improved the five\u2010year CMSS prediction (<jats:italic>P<\/jats:italic>\u2009=\u2009.012) than the one with other covariates only. Further expression quantitative trait loci (eQTL) analysis found that the <jats:italic>LGSN<\/jats:italic> rs12663017 A allele was significantly associated with increased messenger RNA (mRNA) expression levels (<jats:italic>P\u2009=\u2009<\/jats:italic>8.89\u2009\u00d7\u200910\n<jats:sup>\u221211<\/jats:sup>) in lymphoblastoid cell lines of the 1000 Genomes Project database. In the analysis of the genotype tissue expression (GTEx) project datasets, <jats:italic>HAL<\/jats:italic> rs17676826 C and <jats:italic>NOXRED1<\/jats:italic> rs8012548 G alleles were significantly associated with their mRNA expression levels in sun\u2010exposed skin of the lower leg (<jats:italic>P\u2009=\u2009<\/jats:italic>6.62\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup> and 1.37\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>, respectively) and in sun\u2010not\u2010exposed suprapubic skin (<jats:italic>P\u2009&lt;\u2009<\/jats:italic>.001 and 1.43\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>, respectively). Taken together, these genetic variants of glutamine<jats:italic>\u2010<\/jats:italic>metabolic pathway genes may be promising predictors of survival in patients with CM.<\/jats:p>","DOI":"10.1002\/mc.23100","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T07:13:43Z","timestamp":1566458023000},"page":"2091-2103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic variants in glutamine metabolic pathway genes predict cutaneous melanoma\u2010specific survival"],"prefix":"10.1002","volume":"58","author":[{"given":"Ka","family":"Chen","sequence":"first","affiliation":[{"name":"Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine Third Military Medical University  Chongqing China"},{"name":"Duke Cancer Institute Duke University Medical Center  Durham North Carolina"},{"name":"Department of Medicine Duke University School of Medicine  Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center  Durham North Carolina"},{"name":"Department of Medicine Duke University School of Medicine  Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhensheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center  Durham North Carolina"},{"name":"Department of Medicine Duke University School of Medicine  Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Bloomer","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center  Durham North Carolina"},{"name":"Department of Medicine Duke University School of Medicine  Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher I.","family":"Amos","sequence":"additional","affiliation":[{"name":"Department of Community and Family Medicine, Geisel School of Medicine Dartmouth College  Hanover"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology The University of Texas M. D. Anderson Cancer Center  Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Richard M. Fairbanks School of Public Health Indiana University  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmei","family":"Nan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Richard M. Fairbanks School of Public Health Indiana University  Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5265-3930","authenticated-orcid":false,"given":"Qingyi","family":"Wei","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center  Durham North Carolina"},{"name":"Department of Medicine Duke University School of Medicine  Durham North Carolina"},{"name":"Department of Population Health Sciences Duke University School of Medicine  Durham North 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