Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer

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 IversenAndrew 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

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Abstract

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.

Original languageEnglish (US)
Article numbere53903
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 30 2013

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ovarian neoplasms
T-cells
Regulatory T-Lymphocytes
Ovarian Neoplasms
Single Nucleotide Polymorphism
Tumors
T-lymphocytes
Genes
Quantitative Trait Loci
Gene encoding
quantitative trait loci
Immunosuppressive Agents
Polymorphism
immunosuppressive agents
Neoplasms
neoplasms
genes
Nucleotides
RNA
lethal genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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.

In: PLoS One, Vol. 8, No. 1, e53903, 30.01.2013.

Research output: Contribution to journalArticle

Goode, EL, DeRycke, M, Kalli, KR, Oberg, AL, Cunningham, JM, Maurer, MJ, Fridley, BL, Armasu, SM, Serie, DJ, Ramar, P, Goergen, K, Vierkant, RA, Rider, DN, Sicotte, H, Wang, C, Winterhoff, B, Phelan, CM, Schildkraut, JM, Weber, RP, Iversen, E, Berchuck, A, Sutphen, R, Birrer, MJ, Hampras, S, Preus, L, Gayther, SA, Ramus, SJ, Wentzensen, N, Yang, HP, Garcia-Closas, M, Song, H, Tyrer, J, Pharoah, PPD, Konecny, G, Sellers, TA, Ness, RB, Sucheston, LE, Odunsi, K, Hartmann, LC, Moysich, KB & Knutson, KL 2013, 'Inherited Variants in Regulatory T Cell Genes and Outcome of Ovarian Cancer', PLoS One, vol. 8, no. 1, e53903. https://doi.org/10.1371/journal.pone.0053903
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. In: PLoS One. 2013 ; Vol. 8, No. 1.
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abstract = "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.",
author = "Goode, {Ellen L} and Melissa DeRycke and Kalli, {Kimberly R.} and Oberg, {Ann L} and Cunningham, {Julie M} and Maurer, {Matthew J.} and Fridley, {Brooke L.} and Armasu, {Sebastian M.} and Serie, {Daniel J.} and Priya Ramar and Krista Goergen and Vierkant, {Robert A.} and Rider, {David N.} and Hugues Sicotte and Chen Wang and Boris Winterhoff and Phelan, {Catherine M.} and Schildkraut, {Joellen M.} and Weber, {Rachel P.} and Ed Iversen and Andrew Berchuck and Rebecca Sutphen and Birrer, {Michael J.} and Shalaka Hampras and Leah Preus and Gayther, {Simon A.} and Ramus, {Susan J.} and Nicolas Wentzensen and Yang, {Hannah P.} and Montserrat Garcia-Closas and Honglin Song and Jonathan Tyrer and Pharoah, {Paul P D} and Gottfried Konecny and Sellers, {Thomas A.} and Ness, {Roberta B.} and Sucheston, {Lara E.} and Kunle Odunsi and Hartmann, {Lynn C.} and Moysich, {Kirsten B.} and Knutson, {Keith L}",
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AU - Goode, Ellen L

AU - DeRycke, Melissa

AU - Kalli, Kimberly R.

AU - Oberg, Ann L

AU - Cunningham, Julie M

AU - Maurer, Matthew J.

AU - Fridley, Brooke L.

AU - Armasu, Sebastian M.

AU - Serie, Daniel J.

AU - Ramar, Priya

AU - Goergen, Krista

AU - Vierkant, Robert A.

AU - Rider, David N.

AU - Sicotte, Hugues

AU - Wang, Chen

AU - Winterhoff, Boris

AU - Phelan, Catherine M.

AU - Schildkraut, Joellen M.

AU - Weber, Rachel P.

AU - Iversen, Ed

AU - Berchuck, Andrew

AU - Sutphen, Rebecca

AU - Birrer, Michael J.

AU - Hampras, Shalaka

AU - Preus, Leah

AU - Gayther, Simon A.

AU - Ramus, Susan J.

AU - Wentzensen, Nicolas

AU - Yang, Hannah P.

AU - Garcia-Closas, Montserrat

AU - Song, Honglin

AU - Tyrer, Jonathan

AU - Pharoah, Paul P D

AU - Konecny, Gottfried

AU - Sellers, Thomas A.

AU - Ness, Roberta B.

AU - Sucheston, Lara E.

AU - Odunsi, Kunle

AU - Hartmann, Lynn C.

AU - Moysich, Kirsten B.

AU - Knutson, Keith L

PY - 2013/1/30

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