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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.

SUBMITTER: Goode EL 

PROVIDER: S-EPMC3559692 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Goode Ellen L EL   DeRycke Melissa M   Kalli Kimberly R KR   Oberg Ann L AL   Cunningham Julie M JM   Maurer Matthew J MJ   Fridley Brooke L BL   Armasu Sebastian M SM   Serie Daniel J DJ   Ramar Priya P   Goergen Krista K   Vierkant Robert A RA   Rider David N DN   Sicotte Hugues H   Wang Chen C   Winterhoff Boris B   Phelan Catherine M CM   Schildkraut Joellen M JM   Weber Rachel P RP   Iversen Ed E   Berchuck Andrew A   Sutphen Rebecca R   Birrer Michael J MJ   Hampras Shalaka S   Preus Leah L   Gayther Simon A SA   Ramus Susan J SJ   Wentzensen Nicolas N   Yang Hannah P HP   Garcia-Closas Montserrat M   Song Honglin H   Tyrer Jonathan J   Pharoah Paul P D PP   Konecny Gottfried G   Sellers Thomas A TA   Ness Roberta B RB   Sucheston Lara E LE   Odunsi Kunle K   Hartmann Lynn C LC   Moysich Kirsten B KB   Knutson Keith L KL  

PloS one 20130130 1


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 (eQ  ...[more]

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