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

Lara E. Sucheston-Campbell, Rikki Cannioto, Alyssa I. Clay, John Lewis Etter, Kevin H. Eng, Song Liu, Sebastiano Battaglia, Qiang Hu, J. Brian Szender, Albina Minlikeeva, Janine M. Joseph, Paul Mayor, Scott I. Abrams, Brahm H. Segal, Paul K. Wallace, Kah Teong Soh, Emese Zsiros, Hoda Anton-Culver, Elisa V. Bandera, Matthias W. BeckmannAndrew Berchuck, Line Bjorge, Amanda Bruegl, Ian G. Campbell, Shawn Patrice Campbell, Georgia Chenevix-Trench, Daniel W. Cramer, Agnieszka Dansonka Mieszkowska, Fanny Dao, Brenda Diergaarde, Thilo Doerk, Jennifer A. Doherty, Andreas Du Bois, Diana Eccles, Svend Aage Engelholm, Peter A. Fasching, Simon A. Gayther, Aleksandra Gentry-Maharaj, Rosalind M. Glasspool, Marc T. Goodman, Jacek Gronwald, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemmanns, Claus Høgdall, Estrid V.S. Høgdall, Tomasz Huzarski, Allan Jensen, Sharon E. Johnatty, Audrey Jung, Beth Y. Karlan, Reudiger Klapdor, Tomasz Kluz, Bozena Konopka, Susanne Kruger Kjer, Jolanta Kupryjanczyk, Diether Lambrechts, Jenny Lester, Jan Lubinski, Douglas A. Levine, Lene Lundvall, Valerie McGuire, Iain A. McNeish, Usha Menon, Francesmary Modugno, Roberta B. Ness, Sandra Orsulic, James Paul, Celeste Leigh Pearce, Tanja Pejovic, Paul Pharoah, Susan J. Ramus, Joseph Rothstein, Mary Anne Rossing, Matthias Rubner, Joellen M. Schildkraut, Barbara Schmalfeldt, Ira Schwaab, Nadeem Siddiqui, Weiva Sieh, Piotr Sobiczewski, Honglin Song, Kathryn L. Terry, Els Van Nieuwenhuysen, Adriaan Vanderstichele, Ignace Vergote, Christine S. Walsh, Penelope M. Webb, Nicolas Wentzensen, Alice S. Whittemore, Anna H. Wu, Argyrios Ziogas, Kunle Odunsi, Jenny Chang-Claude, Ellen L. Goode, Kirsten B. Moysich

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a 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 and the admixture likelihood method 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 × 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 was not associated with survival in women diagnosed with invasive EOC.

Original languageEnglish (US)
Pages (from-to)420-424
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2017

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Sucheston-Campbell, L. E., Cannioto, R., Clay, A. I., Etter, J. L., Eng, K. H., Liu, S., Battaglia, S., Hu, Q., Brian Szender, J., Minlikeeva, A., Joseph, J. M., Mayor, P., Abrams, S. I., Segal, B. H., Wallace, P. K., Soh, K. T., Zsiros, E., Anton-Culver, H., Bandera, E. V., ... Moysich, K. B. (2017). No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival. Cancer Epidemiology Biomarkers and Prevention, 26(3), 420-424. https://doi.org/10.1158/1055-9965.EPI-16-0631