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Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.
- Source :
-
Oncotarget [Oncotarget] 2016 Oct 25; Vol. 7 (43), pp. 69097-69110. - Publication Year :
- 2016
-
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.<br />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.<br />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).<br />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.
- Subjects :
- Adenocarcinoma, Clear Cell immunology
Adult
Aged
Carcinoma, Ovarian Epithelial
Female
Gene Expression Regulation, Neoplastic
Gene Frequency
Genotype
Humans
Middle Aged
Neoplasms, Glandular and Epithelial immunology
Ovarian Neoplasms immunology
Receptor, Transforming Growth Factor-beta Type II
Risk Factors
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Adenocarcinoma, Clear Cell genetics
Genetic Predisposition to Disease genetics
Neoplasms, Glandular and Epithelial genetics
Ovarian Neoplasms genetics
Polymorphism, Single Nucleotide
Protein Serine-Threonine Kinases genetics
Receptors, Transforming Growth Factor beta genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 43
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 27533245
- Full Text :
- https://doi.org/10.18632/oncotarget.10215