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Impact Journals, Oncotarget, 43(7), p. 69097-69110, 2016

DOI: 10.18632/oncotarget.10215

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

Journal article published in 2016 by Am van Altena, Ss S. Hampras, Rp Weber, As Whittemore, Rikki Cannioto, Jenny Chang-Claude, Francesmary Modugno, Thilo Dörk, Peter Hillemanns, Le E. Sucheston-Campbell, Leah Preus, Kg Wicklund, Lr Wilkens, Ah Wu, Grace Friel and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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