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Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes.

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Date
2015-09
Authors
Fang, Shenying
Wang, Yuling
Chun, Yun S
Liu, Huey
Ross, Merrick I
Gershenwald, Jeffrey E
Cormier, Janice N
Royal, Richard E
Lucci, Anthony
Schacherer, Christopher W
Reveille, John D
Chen, Wei
Sui, Dawen
Bassett, Roland L
Wang, Li-E
Wei, Qingyi
Amos, Christopher I
Lee, Jeffrey E
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(18 total)
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Abstract
Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10(-38)); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10(-9)). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00-2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11-3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome.
Type
Journal article
Subject
Aged
Case-Control Studies
Confidence Intervals
Female
Genetic Predisposition to Disease
Genotype
Humans
Interleukin-12 Subunit p40
Male
Melanoma
Middle Aged
Multivariate Analysis
Polymorphism, Single Nucleotide
Prognosis
Reproducibility of Results
Risk Assessment
Skin Neoplasms
Survival Analysis
Permalink
https://hdl.handle.net/10161/10676
Published Version (Please cite this version)
10.1038/jid.2015.138
Publication Info
Fang, Shenying; Wang, Yuling; Chun, Yun S; Liu, Huey; Ross, Merrick I; Gershenwald, Jeffrey E; ... Lee, Jeffrey E (2015). Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes. J Invest Dermatol, 135(9). pp. 2266-2272. 10.1038/jid.2015.138. Retrieved from https://hdl.handle.net/10161/10676.
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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Scholars@Duke

Wei

Qingyi Wei

Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and
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