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...
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Public Library of Science (PLoS)
2013-01-01
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| author | Ellen L Goode Melissa DeRycke Kimberly R Kalli Ann L Oberg Julie M Cunningham Matthew J Maurer Brooke L Fridley Sebastian M Armasu Daniel J Serie Priya Ramar Krista Goergen Robert A Vierkant David N Rider Hugues Sicotte Chen Wang Boris Winterhoff Catherine M Phelan Joellen M Schildkraut Rachel P Weber Ed Iversen Andrew Berchuck Rebecca Sutphen Michael J Birrer Shalaka Hampras Leah Preus Simon A Gayther Susan J Ramus Nicolas Wentzensen Hannah P Yang Montserrat Garcia-Closas Honglin Song Jonathan Tyrer Paul P D Pharoah Gottfried Konecny Thomas A Sellers Roberta B Ness Lara E Sucheston Kunle Odunsi Lynn C Hartmann Kirsten B Moysich Keith L Knutson |
| author_facet | Ellen L Goode Melissa DeRycke Kimberly R Kalli Ann L Oberg Julie M Cunningham Matthew J Maurer Brooke L Fridley Sebastian M Armasu Daniel J Serie Priya Ramar Krista Goergen Robert A Vierkant David N Rider Hugues Sicotte Chen Wang Boris Winterhoff Catherine M Phelan Joellen M Schildkraut Rachel P Weber Ed Iversen Andrew Berchuck Rebecca Sutphen Michael J Birrer Shalaka Hampras Leah Preus Simon A Gayther Susan J Ramus Nicolas Wentzensen Hannah P Yang Montserrat Garcia-Closas Honglin Song Jonathan Tyrer Paul P D Pharoah Gottfried Konecny Thomas A Sellers Roberta B Ness Lara E Sucheston Kunle Odunsi Lynn C Hartmann Kirsten B Moysich Keith L Knutson |
| author_sort | Ellen L Goode |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-2a05f1d2af3f48b587874e2042946aa9 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-2a05f1d2af3f48b587874e2042946aa92025-08-20T02:05:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5390310.1371/journal.pone.0053903Inherited variants in regulatory T cell genes and outcome of ovarian cancer.Ellen L GoodeMelissa DeRyckeKimberly R KalliAnn L ObergJulie M CunninghamMatthew J MaurerBrooke L FridleySebastian M ArmasuDaniel J SeriePriya RamarKrista GoergenRobert A VierkantDavid N RiderHugues SicotteChen WangBoris WinterhoffCatherine M PhelanJoellen M SchildkrautRachel P WeberEd IversenAndrew BerchuckRebecca SutphenMichael J BirrerShalaka HamprasLeah PreusSimon A GaytherSusan J RamusNicolas WentzensenHannah P YangMontserrat Garcia-ClosasHonglin SongJonathan TyrerPaul P D PharoahGottfried KonecnyThomas A SellersRoberta B NessLara E SuchestonKunle OdunsiLynn C HartmannKirsten B MoysichKeith L KnutsonAlthough 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0053903&type=printable |
| spellingShingle | Ellen L Goode Melissa DeRycke Kimberly R Kalli Ann L Oberg Julie M Cunningham Matthew J Maurer Brooke L Fridley Sebastian M Armasu Daniel J Serie Priya Ramar Krista Goergen Robert A Vierkant David N Rider Hugues Sicotte Chen Wang Boris Winterhoff Catherine M Phelan Joellen M Schildkraut Rachel P Weber Ed Iversen Andrew Berchuck Rebecca Sutphen Michael J Birrer Shalaka Hampras Leah Preus Simon A Gayther Susan J Ramus Nicolas Wentzensen Hannah P Yang Montserrat Garcia-Closas Honglin Song Jonathan Tyrer Paul P D Pharoah Gottfried Konecny Thomas A Sellers Roberta B Ness Lara E Sucheston Kunle Odunsi Lynn C Hartmann Kirsten B Moysich Keith L Knutson Inherited variants in regulatory T cell genes and outcome of ovarian cancer. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0053903&type=printable |
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