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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Fang, S; Wang, Y; Chun, YS; Liu, H; Ross, MI; Gershenwald, JE; Cormier, JN; Royal, RE; Lucci, A; Schacherer, CW; Reveille, JD; Chen, W; Sui, D; Bassett, RL; Wang, L-E; Wei, Q; Amos, CI; Lee, JE

Published Date

  • September 2015

Published In

Volume / Issue

  • 135 / 9

Start / End Page

  • 2266 - 2272

PubMed ID

  • 25848976

Pubmed Central ID

  • 25848976

Electronic International Standard Serial Number (EISSN)

  • 1523-1747

Digital Object Identifier (DOI)

  • 10.1038/jid.2015.138

Language

  • eng

Conference Location

  • United States