No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival
Authors: Sucheston-Campbell Lara E. , Cannioto Rikki , Clay Alyssa I. , Etter John Lewis , Eng Kevin H. , Liu Song , Battaglia Sebastiano , Hu Qiang , Szender J. Brian , Minlikeeva Albina , Joseph Janine M. , Mayor Paul , Abrams Scott I. , Segal Brahm H. , Wallace Paul K. , Soh Kah Teong , Zsiros Emese , Anton-Culver Hoda , Bandera Elisa V. , Beckmann Matthias W. , Berchuck Andrew , Bjorge Line , Bruegl Amanda , Campbell Ian G. , Campbell Shawn Patrice , Chenevix-Trench Georgia , Cramer Daniel W. , Dansonka-Mieszkowska Agnieszka , Dao Fanny , Diergaarde Brenda , Doerk Thilo , Doherty Jennifer A. , du Bois Andreas , Eccles Diana , Engelholm Svend Aage , Fasching Peter A. , Gayther Simon A. , Gentry-Maharaj Aleksandra , Glasspool Rosalind M. , Goodman Marc T. , Gronwald Jacek , Harter Philipp , Hein Alexander , Heitz Florian , Hillemmanns Peter , Høgdall Claus , Høgdall Estrid V.S. , Huzarski Tomasz , Jensen Allan , Johnatty Sharon E. , Jung Audrey , Karlan Beth Y. , Klapdor Reudiger , Kluz Tomasz , Konopka Bożena , Kjær Susanne Krüger , Kupryjanczyk Jolanta , Lambrechts Diether , Lester Jenny , Lubiński Jan , Levine Douglas A. , Lundvall Lene , McGuire Valerie , McNeish Iain A. , Menon Usha , Modugno Francesmary , Ness Roberta B. , Orsulic Sandra , Paul James , Pearce Celeste Leigh , Pejovic Tanja , Pharoah Paul , Ramus Susan J. , Rothstein Joseph , Rossing Mary Anne , Rübner Matthias , Schildkraut Joellen M. , Schmalfeldt Barbara , Schwaab Ira , Siddiqui Nadeem , Sieh Weiva , Sobiczewski Piotr , Song Honglin , Terry Kathryn L. , Van Nieuwenhuysen Els , Vanderstichele Adriaan , Vergote Ignace , Walsh Christine S. , Webb Penelope M. , Wentzensen Nicolas , Whittemore Alice S. , Wu Anna H. , Ziogas Argyrios , Odunsi Kunle , Chang-Claude Jenny , Goode Ellen L. , Moysich Kirsten B. 
Published: September 2016

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 &lt; 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.