title: Inherited variants in regulatory T cell genes and outcome of ovarian cancer.
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.
authors: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America. egoode@mayo.edu
authors: Ellen L
authors: EL
authors: Goode
authors: Melissa
authors: M
authors: DeRycke
authors: Kimberly R
authors: KR
authors: Kalli
authors: Ann L
authors: AL
authors: Oberg
authors: Julie M
authors: JM
authors: Cunningham
authors: Matthew J
authors: MJ
authors: Maurer
authors: Brooke L
authors: BL
authors: Fridley
authors: Sebastian M
authors: SM
authors: Armasu
authors: Daniel J
authors: DJ
authors: Serie
authors: Priya
authors: P
authors: Ramar
authors: Krista
authors: K
authors: Goergen
authors: Robert A
authors: RA
authors: Vierkant
authors: David N
authors: DN
authors: Rider
authors: Hugues
authors: H
authors: Sicotte
authors: Chen
authors: C
authors: Wang
authors: Boris
authors: B
authors: Winterhoff
authors: Catherine M
authors: CM
authors: Phelan
authors: Joellen M
authors: JM
authors: Schildkraut
authors: Rachel P
authors: RP
authors: Weber
authors: Ed
authors: E
authors: Iversen
authors: Andrew
authors: A
authors: Berchuck
authors: Rebecca
authors: R
authors: Sutphen
authors: Michael J
authors: MJ
authors: Birrer
authors: Shalaka
authors: S
authors: Hampras
authors: Leah
authors: L
authors: Preus
authors: Simon A
authors: SA
authors: Gayther
authors: Susan J
authors: SJ
authors: Ramus
authors: Nicolas
authors: N
authors: Wentzensen
authors: Hannah P
authors: HP
authors: Yang
authors: Montserrat
authors: M
authors: Garcia-Closas
authors: Honglin
authors: H
authors: Song
authors: Jonathan
authors: J
authors: Tyrer
authors: Paul P D
authors: PP
authors: Pharoah
authors: Gottfried
authors: G
authors: Konecny
authors: Thomas A
authors: TA
authors: Sellers
authors: Roberta B
authors: RB
authors: Ness
authors: Lara E
authors: LE
authors: Sucheston
authors: Kunle
authors: K
authors: Odunsi
authors: Lynn C
authors: LC
authors: Hartmann
authors: Kirsten B
authors: KB
authors: Moysich
authors: Keith L
authors: KL
authors: Knutson
mesh_terms: D000368:Aged; D000483:Alleles; D018122:B7-1 Antigen / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen
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