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Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes
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 suscept...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580731/ https://www.ncbi.nlm.nih.gov/pubmed/25848976 http://dx.doi.org/10.1038/jid.2015.138 |
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author | 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 |
author_facet | 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 |
author_sort | Fang, Shenying |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4580731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45807312015-10-02 Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes 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 J Invest Dermatol Original 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. Nature Publishing Group 2015-09 2015-05-14 /pmc/articles/PMC4580731/ /pubmed/25848976 http://dx.doi.org/10.1038/jid.2015.138 Text en Copyright © 2015 The Society for Investigative Dermatology, Inc http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Article 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 Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes |
title | Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes |
title_full | Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes |
title_fullStr | Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes |
title_full_unstemmed | Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes |
title_short | Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes |
title_sort | association of common genetic polymorphisms with melanoma patient il-12p40 blood levels, risk, and outcomes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580731/ https://www.ncbi.nlm.nih.gov/pubmed/25848976 http://dx.doi.org/10.1038/jid.2015.138 |
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