Hampras, SS;
Sucheston-Campbell, LE;
Cannioto, R;
Chang-Claude, J;
Modugno, F;
Dörk, T;
Hillemanns, P;
... Moysich, KB; + view all
(2016)
Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.
Oncotarget
, 7
(43)
pp. 69097-69110.
10.18632/oncotarget.10215.
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Abstract
BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.
| Type: | Article |
|---|---|
| Title: | Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.18632/oncotarget.10215 |
| Publisher version: | http://dx.doi.org/10.18632/oncotarget.10215 |
| Language: | English |
| Additional information: | Copyright © 2016 Impact Journals, LLC. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License (CC BY 3.0) (https://creativecommons.org/licenses/by/3.0/) |
| Keywords: | FCGR2B, biomarkers, genetic variation, immunosuppression, ovarian cancer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1508792 |
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