Abstract
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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology |
Vol/bind | 26 |
Udgave nummer | 3 |
Sider (fra-til) | 420-424 |
ISSN | 1055-9965 |
DOI | |
Status | Udgivet - mar. 2017 |
Adgang til dokumentet
Citationsformater
- APA
- Standard
- Harvard
- Vancouver
- Author
- BIBTEX
- RIS
No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival. / 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; Mayor, Paul; Abrams, Scott I; Segal, Brahm; Wallace, Paul K; Soh, Kah Teong; Zsiros, Emese Z; Anton-Culver, Hoda; Bandera, Elisa V; Beckmann, Matthias W; Berchuck, Andrew; Bjørge, Line; Bruegl, Amanda; Campbell, Ian G; Campbell, Shawn Patrice; Chenevix-Trench, Georgia; Cramer, Daniel; 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; Hogdall, Claus; Høgdall, Estrid V S; Huzarski, Tomasz; Jensen, Allan; Johnatty, Sharon E; Jung, Audrey; Karlan, Beth; Klapdor, Rüdiger; Kluz, Tomasz; Konopka, Bozena; Krüger Kjær, Susanne; 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.
I: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Bind 26, Nr. 3, 03.2017, s. 420-424.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
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 -