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

dc.contributor.author Fang, Shenying
dc.contributor.author Wang, Yuling
dc.contributor.author Chun, Yun S
dc.contributor.author Liu, Huey
dc.contributor.author Ross, Merrick I
dc.contributor.author Gershenwald, Jeffrey E
dc.contributor.author Cormier, Janice N
dc.contributor.author Royal, Richard E
dc.contributor.author Lucci, Anthony
dc.contributor.author Schacherer, Christopher W
dc.contributor.author Reveille, John D
dc.contributor.author Chen, Wei
dc.contributor.author Sui, Dawen
dc.contributor.author Bassett, Roland L
dc.contributor.author Wang, Li-E
dc.contributor.author Wei, Qingyi
dc.contributor.author Amos, Christopher I
dc.contributor.author Lee, Jeffrey E
dc.coverage.spatial United States
dc.date.accessioned 2015-10-07T16:42:50Z
dc.date.accessioned 2015-10-07T16:44:58Z
dc.date.issued 2015-09
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/25848976
dc.identifier S0022-202X(15)38992-2
dc.identifier.uri https://hdl.handle.net/10161/10676
dc.description.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.
dc.language eng
dc.publisher Elsevier BV
dc.relation.ispartof J Invest Dermatol
dc.relation.isversionof 10.1038/jid.2015.138
dc.relation.replaces http://hdl.handle.net/10161/10675
dc.relation.replaces 10161/10675
dc.subject Aged
dc.subject Case-Control Studies
dc.subject Confidence Intervals
dc.subject Female
dc.subject Genetic Predisposition to Disease
dc.subject Genotype
dc.subject Humans
dc.subject Interleukin-12 Subunit p40
dc.subject Male
dc.subject Melanoma
dc.subject Middle Aged
dc.subject Multivariate Analysis
dc.subject Polymorphism, Single Nucleotide
dc.subject Prognosis
dc.subject Reproducibility of Results
dc.subject Risk Assessment
dc.subject Skin Neoplasms
dc.subject Survival Analysis
dc.title Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes.
dc.type Journal article
duke.contributor.id Wei, Qingyi|0632334
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/25848976
pubs.begin-page 2266
pubs.end-page 2272
pubs.issue 9
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 135
dc.identifier.eissn 1523-1747
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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