1. No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival.
- Author
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Sucheston-Campbell LE, Cannioto R, Clay AI, Etter JL, Eng KH, Liu S, Battaglia S, Hu Q, Szender JB, Minlikeeva A, Joseph JM, Mayor P, Abrams SI, Segal BH, Wallace PK, Soh KT, Zsiros E, Anton-Culver H, Bandera EV, Beckmann MW, Berchuck A, Bjorge L, Bruegl A, Campbell IG, Campbell SP, Chenevix-Trench G, Cramer DW, Dansonka-Mieszkowska A, Dao F, Diergaarde B, Doerk T, Doherty JA, du Bois A, Eccles D, Engelholm SA, Fasching PA, Gayther SA, Gentry-Maharaj A, Glasspool RM, Goodman MT, Gronwald J, Harter P, Hein A, Heitz F, Hillemmanns P, Høgdall C, Høgdall EV, Huzarski T, Jensen A, Johnatty SE, Jung A, Karlan BY, Klapdor R, Kluz T, Konopka B, Kjær SK, Kupryjanczyk J, Lambrechts D, Lester J, Lubiński J, Levine DA, Lundvall L, McGuire V, McNeish IA, Menon U, Modugno F, Ness RB, Orsulic S, Paul J, Pearce CL, Pejovic T, Pharoah P, Ramus SJ, Rothstein J, Rossing MA, Rübner M, Schildkraut JM, Schmalfeldt B, Schwaab I, Siddiqui N, Sieh W, Sobiczewski P, Song H, Terry KL, Van Nieuwenhuysen E, Vanderstichele A, Vergote I, Walsh CS, Webb PM, Wentzensen N, Whittemore AS, Wu AH, Ziogas A, Odunsi K, Chang-Claude J, Goode EL, and Moysich KB
- Subjects
- Carcinoma, Ovarian Epithelial, Female, Genetic Association Studies, Humans, Neoplasms, Glandular and Epithelial immunology, Ovarian Neoplasms immunology, Genetic Variation, Myeloid-Derived Suppressor Cells immunology, Neoplasms, Glandular and Epithelial genetics, Neoplasms, Glandular and Epithelial mortality, Ovarian Neoplasms genetics, Ovarian Neoplasms mortality
- 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. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. ©2016 AACR ., (©2016 American Association for Cancer Research.)- Published
- 2017
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