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Inherited variants in regulatory T cell genes and outcome of ovarian cancer.

Publication ,  Journal Article
Goode, EL; DeRycke, M; Kalli, KR; Oberg, AL; Cunningham, JM; Maurer, MJ; Fridley, BL; Armasu, SM; Serie, DJ; Ramar, P; Goergen, K; Rider, DN ...
Published in: PLoS One
2013

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

1

Start / End Page

e53903

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Middle Aged
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic
 

Citation

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Chicago
ICMJE
MLA
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Goode, E. L., DeRycke, M., Kalli, K. R., Oberg, A. L., Cunningham, J. M., Maurer, M. J., … Knutson, K. L. (2013). Inherited variants in regulatory T cell genes and outcome of ovarian cancer. PLoS One, 8(1), e53903. https://doi.org/10.1371/journal.pone.0053903
Goode, Ellen L., Melissa DeRycke, Kimberly R. Kalli, Ann L. Oberg, Julie M. Cunningham, Matthew J. Maurer, Brooke L. Fridley, et al. “Inherited variants in regulatory T cell genes and outcome of ovarian cancer.PLoS One 8, no. 1 (2013): e53903. https://doi.org/10.1371/journal.pone.0053903.
Goode EL, DeRycke M, Kalli KR, Oberg AL, Cunningham JM, Maurer MJ, et al. Inherited variants in regulatory T cell genes and outcome of ovarian cancer. PLoS One. 2013;8(1):e53903.
Goode, Ellen L., et al. “Inherited variants in regulatory T cell genes and outcome of ovarian cancer.PLoS One, vol. 8, no. 1, 2013, p. e53903. Pubmed, doi:10.1371/journal.pone.0053903.
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. Inherited variants in regulatory T cell genes and outcome of ovarian cancer. PLoS One. 2013;8(1):e53903.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

1

Start / End Page

e53903

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Middle Aged
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic