Goode, EL;
Derycke, M;
Kalli, KR;
Oberg, AL;
Cunningham, JM;
Maurer, MJ;
Fridley, BL;
... Knutson, KL; + view all
(2013)
Inherited variants in regulatory T cell genes and outcome of ovarian cancer.
PLoS One
, 8
(1)
, Article e53903. 10.1371/journal.pone.0053903.
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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.
| Type: | Article |
|---|---|
| Title: | Inherited variants in regulatory T cell genes and outcome of ovarian cancer. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0053903 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0053903 |
| Language: | English |
| Additional information: | © 2013 Goode et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The scientific development and funding for this project were supported in part by the Mayo Clinic Ovarian Cancer SPORE (P50-CA136393) to ELG, LCH, and KLK, the National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112), National Cancer Institute Research project grants (R01-CA086888, R01-CA122443, R01-CA106414, R01-CA76016, R01-CA114343), Cancer Research United Kingdom (A10119, A10124, A8339, A6187, A11306, A7058), the Medical Research Council (G0801875–89310), the Ovarian Cancer Research Fund, the Mayo Foundation, the Minnesota Ovarian Cancer Alliance, the Mayo Foundation, the Roswell Park Cancer Institute Alliance Foundation, and the Fred C. and Katherine B. Andersen Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1385312 |
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