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

Hampras, S. S. et al. (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. (doi:10.18632/oncotarget.10215) (PMID:27533245)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Paul, Mr James and Carty, Mrs Karen and Mcneish, Professor Iain and Glasspool, Dr Rosalind
Authors: Hampras, S. S., Sucheston-Campbell, L. E., Cannioto, R., Chang-Claude, J., Modugno, F., Dörk, 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., Schoof, N., Eng, K. H., Clay, A., Singh, P. K., Joseph, J. M., Aben, K. K.H., Anton-Culver, H., Antonenkova, N., Baker, H., Bean, Y., Beckmann, M. W., Bisogna, M., Bjorge, L., Bogdanova, N., Brinton, L. A., Brooks-Wilson, A., Bruinsma, F., Butzow, R., Campbell, I. G., Carty, K., Cook, L. S., Cramer, D. W., Cybulski, C., Dansonka-Mieszkowska, A., Dennis, J., Despierre, E., Dicks, E., Doherty, J. A., du Bois, A., Dürst, M., Easton, D., Eccles, D., Edwards, R. P., Ekici, A. B., Fasching, P. A., Fridley, B. L., Gao, Y.-T., Gentry-Maharaj, A., Giles, G. G., Glasspool, R., Gronwald, J., Harrington, P., Harter, P., Hasmad, H. N., Hein, A., Heitz, F., Hildebrandt, M. A.T., Hogdall, C., Hogdall, E., Hosono, S., Iversen, E. S., Jakubowska, A., Jensen, A., Ji, B.-T., Karlan, B. Y., Kellar, M., Kelley, J. L., Kiemeney, L. A., Klapdor, R., Kolomeyevskaya, N., Krakstad, C., Kjaer, S. K., Kruszka, B., Kupryjanczyk, J., Lambrechts, D., Lambrechts, S., Le, N. D., Lee, A. W., Lele, S., Leminen, A., Lester, J., Levine, D. A., Liang, D., Lissowska, J., Liu, S., Lu, K., Lubinski, J., Lundvall, L., Massuger, L. F.A.G., Matsuo, K., McGuire, V., McLaughlin, J. R., Mcneish, I., Menon, U., Moes-Sosnowska, J., Narod, S. A., Nedergaard, L., Nevalinna, H., Nickels, S., Nedergaard, L., Nevanlinna, H., Nickels, S., Olson, S. H., Orlow, I., Weber, R. P., Paul, J., Pejovic, T., Pelttari, L. M., Perkins, B., Permuth-Wey, J., Pike, M. C., Plisiecka-Halasa, J., Poole, E. M., Risch, H. A., Rossing, M. A., Rothstein, J. H., Rudolph, A., Runnebaum, I. B., Rzepecka, I. K., Salvesen, H. B., Schernhammer, E., Schmitt, K., Schwaab, I., Shu, X.-O., Shvetsov, Y. B., Siddiqui, N., Sieh, W., Song, H., Southey, M. C., Tangen, I. L., Teo, S.-H., Thompson, P. J., Timorek, A., Tsai, Y.-Y., Tworoger, S. S., Tyrer, J., van Altena, A. M., Vergote, I., Vierkant, R. A., Walsh, C., Wang-Gohrke, S., Wentzensen, N., Whittemore, A. S., Wicklund, K. G., Wilkens, L. R., Wu, A. H., Wu, X., Woo, Y.-L., Yang, H., Zheng, W., Ziogas, A., Gayther, S. A., Ramus, S. J., Sellers, T. A., Schildkraut, J. M., Phelan, C. M., Berchuck, A., Chenevix-Trench, G., Cunningham, J. M., Pharoah, P. P., Ness, R. B., Odunsi, K., Goode, E. L., and Moysich, K. B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Oncotarget
Publisher:Impact Journals
ISSN:1949-2553
ISSN (Online):1949-2553
Published Online:21 June 2016

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