Year: 2013
Type: article
Study design: Observational Study
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.
Source: PLoS ONE
Authors: 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
Institutions: Mayo Clinic, University of South Florida, Moffitt Cancer Center, Duke University, Duke Medical Center, Brigham and Women's Hospital, Harvard University, Roswell Park Comprehensive Cancer Center, University of Southern California, National Institutes of Health, National Cancer Institute, Institute of Cancer Research, University of Cambridge, University of California, Los Angeles, Mayo Clinic Comprehensive Cancer Center (Minnesota)
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1440585907, G1574184113, G1651137428, G1791794685, G1849757321, G1885355073, G19362627, G2026970617, G2028771710, Population-Based Analysis of Ovarian Cancer Biomarkers, The Molecular Epidemiology Of Ovarian Cancer, G3695179805, G3695342494, G3918072604, Estrogen Bioactivation and Risk of Ovarian Cancer, G401803774, G4061461591, G4119975330, G4232426906, G4713782523, G5082594465, G6179720485, G6208597191, G6283257732, G6433449787, G7009610138, G7326189359, Genetic Variation in the NF-kappaB Pathway and Ovarian Cancer Etiology, The Mitochondrial Genome and Ovarian Cancer Risk, G8344375360, G8386849510, G8405173764, Haplotype-Based Genome Screen for Ovarian Cancer Loci, Mayo Clinic Comprehensive Cancer Center Support Grant, G998640432
OpenAlex ID: W2047495852