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

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    Author
    Hampras, SS; Sucheston-Campbell, LE; Cannioto, R; Chang-Claude, J; Modugno, F; Doerk, T; Hillemanns, P; Preus, L; Knutson, KL; Wallace, PK; ...
    Date
    2016-10-25
    Source Title
    Oncotarget
    Publisher
    IMPACT JOURNALS LLC
    University of Melbourne Author/s
    Campbell, Ian; Southey, Melissa; Ramus, Susan; Bruinsma, Fiona; Giles, Graham; Baglietto, Laura
    Affiliation
    Melbourne School of Population and Global Health
    Sir Peter MacCallum Department of Oncology
    Clinical Pathology
    Metadata
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    Document Type
    Journal Article
    Citations
    Hampras, S. S., Sucheston-Campbell, L. E., Cannioto, R., Chang-Claude, J., Modugno, F., Doerk, T., Hillemanns, P., Preus, L., Knutson, K. L., Wallace, P. K., Hong, C. -C., Friel, G., Davis, W., Nesline, M., Pearce, C. L., Kelemen, L. E., Goodman, M. T., Bandera, E. V., Terry, K. L. ,... Moysich, K. B. (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. https://doi.org/10.18632/oncotarget.10215.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256412
    DOI
    10.18632/oncotarget.10215
    NHMRC Grant code
    NHMRC/400413
    NHMRC/400281
    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.

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