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Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer
Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559692/ https://www.ncbi.nlm.nih.gov/pubmed/23382860 http://dx.doi.org/10.1371/journal.pone.0053903 |
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author | Goode, Ellen L. DeRycke, Melissa Kalli, Kimberly R. Oberg, Ann L. Cunningham, Julie M. Maurer, Matthew J. Fridley, Brooke L. Armasu, Sebastian M. Serie, Daniel J. Ramar, Priya Goergen, Krista Vierkant, Robert A. Rider, David N. Sicotte, Hugues Wang, Chen Winterhoff, Boris Phelan, Catherine M. Schildkraut, Joellen M. Weber, Rachel P. Iversen, Ed Berchuck, Andrew Sutphen, Rebecca Birrer, Michael J. Hampras, Shalaka Preus, Leah Gayther, Simon A. Ramus, Susan J. Wentzensen, Nicolas Yang, Hannah P. Garcia-Closas, Montserrat Song, Honglin Tyrer, Jonathan Pharoah, Paul P. D. Konecny, Gottfried Sellers, Thomas A. Ness, Roberta B. Sucheston, Lara E. Odunsi, Kunle Hartmann, Lynn C. Moysich, Kirsten B. Knutson, Keith L. |
author_facet | Goode, Ellen L. DeRycke, Melissa Kalli, Kimberly R. Oberg, Ann L. Cunningham, Julie M. Maurer, Matthew J. Fridley, Brooke L. Armasu, Sebastian M. Serie, Daniel J. Ramar, Priya Goergen, Krista Vierkant, Robert A. Rider, David N. Sicotte, Hugues Wang, Chen Winterhoff, Boris Phelan, Catherine M. Schildkraut, Joellen M. Weber, Rachel P. Iversen, Ed Berchuck, Andrew Sutphen, Rebecca Birrer, Michael J. Hampras, Shalaka Preus, Leah Gayther, Simon A. Ramus, Susan J. Wentzensen, Nicolas Yang, Hannah P. Garcia-Closas, Montserrat Song, Honglin Tyrer, Jonathan Pharoah, Paul P. D. Konecny, Gottfried Sellers, Thomas A. Ness, Roberta B. Sucheston, Lara E. Odunsi, Kunle Hartmann, Lynn C. Moysich, Kirsten B. Knutson, Keith L. |
author_sort | Goode, Ellen L. |
collection | PubMed |
description | Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7×10(−5)), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10(−4), and rs3753348, p = 9.0×10(−4), respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10(−4)). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1×10(−4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies. |
format | Online Article Text |
id | pubmed-3559692 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35596922013-02-04 Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer Goode, Ellen L. DeRycke, Melissa Kalli, Kimberly R. Oberg, Ann L. Cunningham, Julie M. Maurer, Matthew J. Fridley, Brooke L. Armasu, Sebastian M. Serie, Daniel J. Ramar, Priya Goergen, Krista Vierkant, Robert A. Rider, David N. Sicotte, Hugues Wang, Chen Winterhoff, Boris Phelan, Catherine M. Schildkraut, Joellen M. Weber, Rachel P. Iversen, Ed Berchuck, Andrew Sutphen, Rebecca Birrer, Michael J. Hampras, Shalaka Preus, Leah Gayther, Simon A. Ramus, Susan J. Wentzensen, Nicolas Yang, Hannah P. Garcia-Closas, Montserrat Song, Honglin Tyrer, Jonathan Pharoah, Paul P. D. Konecny, Gottfried Sellers, Thomas A. Ness, Roberta B. Sucheston, Lara E. Odunsi, Kunle Hartmann, Lynn C. Moysich, Kirsten B. Knutson, Keith L. PLoS One Research Article Although ovarian cancer is the most lethal of gynecologic malignancies, wide variation in outcome following conventional therapy continues to exist. The presence of tumor-infiltrating regulatory T cells (Tregs) has a role in outcome of this disease, and a growing body of data supports the existence of inherited prognostic factors. However, the role of inherited variants in genes encoding Treg-related immune molecules has not been fully explored. We analyzed expression quantitative trait loci (eQTL) and sequence-based tagging single nucleotide polymorphisms (tagSNPs) for 54 genes associated with Tregs in 3,662 invasive ovarian cancer cases. With adjustment for known prognostic factors, suggestive results were observed among rarer histological subtypes; poorer survival was associated with minor alleles at SNPs in RGS1 (clear cell, rs10921202, p = 2.7×10(−5)), LRRC32 and TNFRSF18/TNFRSF4 (mucinous, rs3781699, p = 4.5×10(−4), and rs3753348, p = 9.0×10(−4), respectively), and CD80 (endometrioid, rs13071247, p = 8.0×10(−4)). Fo0r the latter, correlative data support a CD80 rs13071247 genotype association with CD80 tumor RNA expression (p = 0.006). An additional eQTL SNP in CD80 was associated with shorter survival (rs7804190, p = 8.1×10(−4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies. Public Library of Science 2013-01-30 /pmc/articles/PMC3559692/ /pubmed/23382860 http://dx.doi.org/10.1371/journal.pone.0053903 Text en © 2013 Goode et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Goode, Ellen L. DeRycke, Melissa Kalli, Kimberly R. Oberg, Ann L. Cunningham, Julie M. Maurer, Matthew J. Fridley, Brooke L. Armasu, Sebastian M. Serie, Daniel J. Ramar, Priya Goergen, Krista Vierkant, Robert A. Rider, David N. Sicotte, Hugues Wang, Chen Winterhoff, Boris Phelan, Catherine M. Schildkraut, Joellen M. Weber, Rachel P. Iversen, Ed Berchuck, Andrew Sutphen, Rebecca Birrer, Michael J. Hampras, Shalaka Preus, Leah Gayther, Simon A. Ramus, Susan J. Wentzensen, Nicolas Yang, Hannah P. Garcia-Closas, Montserrat Song, Honglin Tyrer, Jonathan Pharoah, Paul P. D. Konecny, Gottfried Sellers, Thomas A. Ness, Roberta B. Sucheston, Lara E. Odunsi, Kunle Hartmann, Lynn C. Moysich, Kirsten B. Knutson, Keith L. Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer |
title | Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer |
title_full | Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer |
title_fullStr | Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer |
title_full_unstemmed | Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer |
title_short | Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer |
title_sort | inherited variants in regulatory t cell genes and outcome of ovarian cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559692/ https://www.ncbi.nlm.nih.gov/pubmed/23382860 http://dx.doi.org/10.1371/journal.pone.0053903 |
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