Assessment of variation in immunosuppressive pathway genes reveals TGFBR2/risk of clear cell ovarian cancer Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Thursday, August 18, 2016

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2/risk of clear cell ovarian cancer




What are T regulatory cells?
The regulatory T cells (Tregs), formerly known as suppressor T cells, are a subpopulation of T cells which modulate the immune system, maintain tolerance to self-antigens, and abrogate autoimmune disease. These cells generally suppress or downregulate induction and proliferation of effector T cells.

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open access:
Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

 Table 1: Descriptive characteristics of 15,596 ovarian cancer cases and 23,236 controls from the Ovarian Cancer Association Consortium (OCAC)






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, serous and high-grade serous, respectively), IL8RA (endometrioid and mucinous), LGALS1 ( mucinous), STAT5B (clear cell), TGFBR1 (endometrioid) and TGFBR2 (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.

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