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 Joseph; Paul Mayor; Scott I Abrams; Brahm Segal; Paul K Wallace; Kah Teong Soh; Emese Z Zsiros; Hoda Anton-Culver; Elisa V Bandera; Matthias W Beckmann; Andrew Berchuck; Line Bjørge; Amanda Bruegl; Ian G Campbell; Shawn Patrice Campbell; Georgia Chenevix-Trench; Daniel 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 Hogdall; Estrid V S Høgdall; Tomasz Huzarski; Allan Jensen; Sharon E Johnatty; Audrey Jung; Beth Karlan; Rüdiger Klapdor; Tomasz Kluz; Bozena Konopka; Susanne Krüger Kjær; Jolanta Kupryjanczyk; Diether Lambrechts; Jenny Lester; Jan Lubiński; 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 Rübner; 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

doi:10.1158/1055-9965.epi-16-0631

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 Joseph, Paul Mayor, Scott I Abrams, Brahm Segal, Paul K Wallace, Kah Teong Soh, Emese Z Zsiros, Hoda Anton-Culver, Elisa V Bandera, Matthias W BeckmannAndrew Berchuck, Line Bjørge, Amanda Bruegl, Ian G Campbell, Shawn Patrice Campbell, Georgia Chenevix-Trench, Daniel 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 Hogdall, Estrid V S Høgdall, Tomasz Huzarski, Allan Jensen, Sharon E Johnatty, Audrey Jung, Beth Karlan, Rüdiger Klapdor, Tomasz Kluz, Bozena Konopka, Susanne Krüger Kjær, Jolanta Kupryjanczyk, Diether Lambrechts, Jenny Lester, Jan Lubiński, 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 Rübner, 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

Department of Clinical Medicine

3 Citations (Scopus)

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 language	English
Journal	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume	26
Issue number	3
Pages (from-to)	420-424
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.epi-16-0631
Publication status	Published - 1 Mar 2017

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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., Szender, J. B., Minlikeeva, A., Joseph, J., Mayor, P., Abrams, S. I., Segal, B., Wallace, P. K., Soh, K. T., Zsiros, E. Z., 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 & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 26(3), 420-424. https://doi.org/10.1158/1055-9965.epi-16-0631

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 et al.

In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Vol. 26, No. 3, 01.03.2017, p. 420-424.

Research output: Contribution to journal › Journal article › Research › peer-review

Sucheston-Campbell, LE, Cannioto, R, Clay, AI, Etter, JL, Eng, KH, Liu, S, Battaglia, S, Hu, Q, Szender, JB, Minlikeeva, A, Joseph, J, Mayor, P, Abrams, SI, Segal, B, Wallace, PK, Soh, KT, Zsiros, EZ, Anton-Culver, H, Bandera, EV, Beckmann, MW, Berchuck, A, Bjørge, L, Bruegl, A, Campbell, IG, Campbell, SP, Chenevix-Trench, G, Cramer, D, 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, Hogdall, C , Høgdall, EVS, Huzarski, T, Jensen, A, Johnatty, SE, Jung, A, Karlan, B, Klapdor, R, Kluz, T, Konopka, B, Krüger Kjær, S, 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 & Moysich, KB 2017, 'No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival', Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol. 26, no. 3, pp. 420-424. https://doi.org/10.1158/1055-9965.epi-16-0631

Sucheston-Campbell LE, Cannioto R, Clay AI, Etter JL, Eng KH, Liu S et al. No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2017 Mar 1;26(3):420-424. doi: 10.1158/1055-9965.epi-16-0631

Sucheston-Campbell, Lara E ; Cannioto, Rikki ; Clay, Alyssa I et al. / No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival. In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2017 ; Vol. 26, No. 3. pp. 420-424.

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

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.",

author = "Sucheston-Campbell, {Lara E} and Rikki Cannioto and Clay, {Alyssa I} and Etter, {John Lewis} and Eng, {Kevin H} and Song Liu and Sebastiano Battaglia and Qiang Hu and Szender, {J Brian} and Albina Minlikeeva and Janine Joseph and Paul Mayor and Abrams, {Scott I} and Brahm Segal and Wallace, {Paul K} and Soh, {Kah Teong} and Zsiros, {Emese Z} and Hoda Anton-Culver and Bandera, {Elisa V} and Beckmann, {Matthias W} and Andrew Berchuck and Line Bj{\o}rge and Amanda Bruegl and Campbell, {Ian G} and Campbell, {Shawn Patrice} and Georgia Chenevix-Trench and Daniel Cramer and Agnieszka Dansonka-Mieszkowska and Fanny Dao and Brenda Diergaarde and Thilo Doerk and Doherty, {Jennifer A} and {du Bois}, Andreas and Diana Eccles and Engelholm, {Svend Aage} and Fasching, {Peter A} and Gayther, {Simon A} and Aleksandra Gentry-Maharaj and Glasspool, {Rosalind M} and Goodman, {Marc T} and Jacek Gronwald and Philipp Harter and Alexander Hein and Florian Heitz and Peter Hillemmanns and Claus Hogdall and H{\o}gdall, {Estrid V S} and Tomasz Huzarski and Allan Jensen and Johnatty, {Sharon E} and Audrey Jung and Beth Karlan and R{\"u}diger Klapdor and Tomasz Kluz and Bozena Konopka and {Kr{\"u}ger Kj{\ae}r}, Susanne and Jolanta Kupryjanczyk and Diether Lambrechts and Jenny Lester and Jan Lubi{\'n}ski and Levine, {Douglas A} and Lene Lundvall and Valerie McGuire and McNeish, {Iain A} and Usha Menon and Francesmary Modugno and Ness, {Roberta B} and Sandra Orsulic and James Paul and Pearce, {Celeste Leigh} and Tanja Pejovic and Paul Pharoah and Ramus, {Susan J} and Joseph Rothstein and Rossing, {Mary Anne} and Matthias R{\"u}bner and Schildkraut, {Joellen M} and Barbara Schmalfeldt and Ira Schwaab and Nadeem Siddiqui and Weiva Sieh and Piotr Sobiczewski and Honglin Song and Terry, {Kathryn L} and {Van Nieuwenhuysen}, Els and Adriaan Vanderstichele and Ignace Vergote and Walsh, {Christine S} and Webb, {Penelope M} and Nicolas Wentzensen and Whittemore, {Alice S} and Wu, {Anna H} and Argyrios Ziogas and Kunle Odunsi and Jenny Chang-Claude and Goode, {Ellen L} and Moysich, {Kirsten B}",

note = "Copyright {copyright, serif}2016, American Association for Cancer Research.",

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doi = "10.1158/1055-9965.epi-16-0631",

language = "English",

volume = "26",

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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

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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.

AB - 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.

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

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

M3 - Journal article

C2 - 27677730

SN - 1055-9965

VL - 26

SP - 420

EP - 424

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 3

ER -

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

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