TY - JOUR

T1 - No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival

AU - Sucheston-Campbell, Lara E

AU - Cannioto, Rikki

AU - Clay, Alyssa I

AU - Etter, John Lewis

AU - Eng, Kevin H

AU - Liu, Song

AU - Battaglia, Sebastiano

AU - Hu, Qiang

AU - Szender, J Brian

AU - Minlikeeva, Albina

AU - Joseph, Janine

AU - Mayor, Paul

AU - Abrams, Scott I

AU - Segal, Brahm

AU - Wallace, Paul K

AU - Soh, Kah Teong

AU - Zsiros, Emese Z

AU - Anton-Culver, Hoda

AU - Bandera, Elisa V

AU - Beckmann, Matthias W

AU - Berchuck, Andrew

AU - Bjørge, Line

AU - Bruegl, Amanda

AU - Campbell, Ian G

AU - Campbell, Shawn Patrice

AU - Chenevix-Trench, Georgia

AU - Cramer, Daniel

AU - Dansonka-Mieszkowska, Agnieszka

AU - Dao, Fanny

AU - Diergaarde, Brenda

AU - Doerk, Thilo

AU - Doherty, Jennifer A

AU - du Bois, Andreas

AU - Eccles, Diana

AU - Engelholm, Svend Aage

AU - Fasching, Peter A

AU - Gayther, Simon A

AU - Gentry-Maharaj, Aleksandra

AU - Glasspool, Rosalind M

AU - Goodman, Marc T

AU - Gronwald, Jacek

AU - Harter, Philipp

AU - Hein, Alexander

AU - Heitz, Florian

AU - Hillemmanns, Peter

AU - Hogdall, Claus

AU - Høgdall, Estrid V S

AU - Huzarski, Tomasz

AU - Jensen, Allan

AU - Johnatty, Sharon E

AU - Jung, Audrey

AU - Karlan, Beth

AU - Klapdor, Rüdiger

AU - Kluz, Tomasz

AU - Konopka, Bozena

AU - Krüger Kjær, Susanne

AU - Kupryjanczyk, Jolanta

AU - Lambrechts, Diether

AU - Lester, Jenny

AU - Lubiński, Jan

AU - Levine, Douglas A

AU - Lundvall, Lene

AU - McGuire, Valerie

AU - McNeish, Iain A

AU - Menon, Usha

AU - Modugno, Francesmary

AU - Ness, Roberta B

AU - Orsulic, Sandra

AU - Paul, James

AU - Pearce, Celeste Leigh

AU - Pejovic, Tanja

AU - Pharoah, Paul

AU - Ramus, Susan J

AU - Rothstein, Joseph

AU - Rossing, Mary Anne

AU - Rübner, Matthias

AU - Schildkraut, Joellen M

AU - Schmalfeldt, Barbara

AU - Schwaab, Ira

AU - Siddiqui, Nadeem

AU - Sieh, Weiva

AU - Sobiczewski, Piotr

AU - Song, Honglin

AU - Terry, Kathryn L

AU - Van Nieuwenhuysen, Els

AU - Vanderstichele, Adriaan

AU - Vergote, Ignace

AU - Walsh, Christine S

AU - Webb, Penelope M

AU - Wentzensen, Nicolas

AU - Whittemore, Alice S

AU - Wu, Anna H

AU - Ziogas, Argyrios

AU - Odunsi, Kunle

AU - Chang-Claude, Jenny

AU - Goode, Ellen L

AU - Moysich, Kirsten B

N1 - Copyright {copyright, serif}2016, American Association for Cancer Research.

PY - 2017/3

Y1 - 2017/3

N2 - 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.

AB - 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.

U2 - 10.1158/1055-9965.EPI-16-0631

DO - 10.1158/1055-9965.EPI-16-0631

M3 - Journal article

C2 - 27677730

VL - 26

SP - 420

EP - 424

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 3

ER -