No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival

Sucheston-Campbell, L. E. et al. (2017) No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival. Cancer Epidemiology, Biomarkers and Prevention, 26(3), pp. 420-424. (doi: 10.1158/1055-9965.EPI-16-0631) (PMID:27677730) (PMCID:PMC5500198)

123527.pdf - Accepted Version



Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immune suppressive/pro-tumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be one prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association study (VEGAS) and the Admixture Likelihood method (AML), were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (p<3.5 x 10-5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs were not associated with survival in women diagnosed with invasive EOC.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Paul, Mr James and Mcneish, Professor Iain and Glasspool, Dr Rosalind
Authors: Sucheston-Campbell, L. E., Cannioto, R., Clay, A. I., Etter, J. L., Eng, K. H., Liu, S., Battaglia, S., Hu, Q., Szender, J. B., Minlikeeva, A., Joseph, J. M., Mayor, P., Abrams, S. I., Segal, B., Wallace, P. K., Soh, K. T., Zsiros, E. Z., Anton-Culver, H., Bandera, E. V., Beckmann, M. W., Berchuck, A., Bjørge, L., Bruegl, A., Campbell, I. G., Campbell, S. P., Chenevix-Trench, G., Cramer, D., Dansonka-Mieszkowska, A., Dao, F., Diergaarde, B., Doerk, T., Doherty, J. A., du Bois, A., Eccles, D., Engelholm, S. A., Fasching, P. A., Gayther, S. A., Gentry-Maharaj, A., Glasspool, R. M., Goodman, M. T., Gronwald, J., Harter, P., Hein, A., Heitz, F., Hillemmanns, P., Høgdall, C., Høgdall, E. V.S., Huzarski, T., Jensen, A., Johnatty, S. E., Jung, A., Karlan, B., Klapdor, R., Kluz, T., Konopka, B., Kjær, S. K., Kupryjanczyk, J., Lambrechts, D., Lester, J., Lubiński, J., Levine, D. A., Lundvall, L., McGuire, V., McNeish, I. A., Menon, U., Modugno, F., Ness, R. B., Orsulic, S., Paul, J., Pearce, C. L., Pejovic, T., Pharoah, P., Ramus, S. J., Rothstein, J., Rossing, M. A., Rübner, M., Schildkraut, J. M., Schmalfeldt, B., Schwaab, I., Siddiqui, N., Sieh, W., Sobiczewski, P., Song, H., Terry, K. L., Van Nieuwenhuysen, E., Vanderstichele, A., Vergote, I., Walsh, C. S., Webb, P. M., Wentzensen, N., Whittemore, A. S., Wu, A. H., Ziogas, A., Odunsi, K., Chang-Claude, J., Goode, E. L., and Moysich, K. B.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Cancer Epidemiology, Biomarkers and Prevention
Publisher:American Association for Cancer Research
ISSN (Online):1538-7755
Published Online:27 September 2016
Copyright Holders:Copyright © 2016 American Association for Cancer Research
First Published:First published in Cancer Epidemiology, Biomarkers and Prevention 26(3): 420-424
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
415281Pharmacodynamics and drug resistanceRobert BrownCancer Research UK (CAN-RES-UK)C536/A6689RI CANCER SCIENCES