TY - JOUR
T1 - Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes
AU - Fang, Shenying
AU - Wang, Yuling
AU - Chun, Yun S.
AU - Liu, Huey
AU - Ross, Merrick I.
AU - Gershenwald, Jeffrey E.
AU - Cormier, Janice N.
AU - Royal, Richard E.
AU - Lucci, Anthony
AU - Schacherer, Christopher W.
AU - Reveille, John D.
AU - Chen, Wei
AU - Sui, Dawen
AU - Bassett, Roland L.
AU - Wang, Li E.
AU - Wei, Qingyi
AU - Amos, Christopher I.
AU - Lee, Jeffrey E.
N1 - Publisher Copyright:
© 2015 The Society for Investigative Dermatology.
PY - 2015/9/18
Y1 - 2015/9/18
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2015.138
DO - 10.1038/jid.2015.138
M3 - Article
C2 - 25848976
AN - SCOPUS:84939463494
SN - 0022-202X
VL - 135
SP - 2266
EP - 2272
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -