Common variants at 19p13 are associated with susceptibility to ovarian cancer

Kelly L. Bolton; Jonathan Tyrer; Honglin Song; Susan J. Ramus; Maria Notaridou; Chris Jones; Tanya Sher; Aleksandra Gentry-Maharaj; Eva Wozniak; Ya Yu Tsai; Joanne Weidhaas; Daniel Paik; David J. Van Den Berg; Daniel O. Stram; Celeste Leigh Pearce; Anna H. Wu; Wendy Brewster; Hoda Anton-Culver; Argyrios Ziogas; Steven A. Narod; Douglas A. Levine; Stanley B. Kaye; Robert Brown; Jim Paul; James Flanagan; Weiva Sieh; Valerie McGuire; Alice S. Whittemore; Ian Campbell; Martin E. Gore; Jolanta Lissowska; Hanna P. Yang; Krzysztof Medrek; Jacek Gronwald; Jan Lubinski; Anna Jakubowska; Nhu D. Le; Linda S. Cook; Linda E. Kelemen; Angela Brook-Wilson; Leon F.A.G. Massuger; Lambertus A. Kiemeney; Katja K.H. Aben; Anne M. Van Altena; Richard Houlston; Ian Tomlinson; Rachel T. Palmieri; Patricia G. Moorman; Joellen Schildkraut; Edwin S. Iversen; Catherine Phelan; Robert A. Vierkant; Julie M. Cunningham; Ellen L. Goode; Brooke L. Fridley; Susan Kruger-Kjaer; Jan Blaeker; Estrid Hogdall; Claus Hogdall; Jenny Gross; Beth Y. Karlan; Roberta B. Ness; Robert P. Edwards; Kunle Odunsi; Kirsten B. Moyisch; Julie A. Baker; Francesmary Modugno; Tuomas Heikkinenen; Ralf Butzow; Heli Nevanlinna; Arto Leminen; Natalia Bogdanova; Natalia Antonenkova; Thilo Doerk; Peter Hillemanns; Matthias Dürst; Ingo Runnebaum; Pamela J. Thompson; Michael E. Carney; Marc T. Goodman; Galina Lurie; Shan Wang-Gohrke; Rebecca Hein; Jenny Chang-Claude; Mary Anne Rossing; Kara L. Cushing-Haugen; Jennifer Doherty; Chu Chen; Thorunn Rafnar; Soren Besenbacher; Patrick Sulem; Kari Stefansson; Michael J. Birrer; Kathryn L. Terry; Dena Hernandez; Daniel W. Cramer; Ignace Vergote; Frederic Amant; Diether Lambrechts; Evelyn Despierre; Peter A. Fasching; Matthias W. Beckmann; Falk C. Thiel; Arif B. Ekici; Xiaoqing Chen; Sharon E. Johnatty; Penelope M. Webb; Jonathan Beesley; Stephen Chanock; Montserrat Garcia-Closas; Tom Sellers; Douglas F. Easton; Andrew Berchuck; Georgia Chenevix-Trench; Paul D.P. Pharoah; Simon A. Gayther

doi:10.1038/ng.666

Common variants at 19p13 are associated with susceptibility to ovarian cancer

Kelly L. Bolton, Jonathan Tyrer, Honglin Song, Susan J. Ramus, Maria Notaridou, Chris Jones, Tanya Sher, Aleksandra Gentry-Maharaj, Eva Wozniak, Ya Yu Tsai, Joanne Weidhaas, Daniel Paik, David J. Van Den Berg, Daniel O. Stram, Celeste Leigh Pearce, Anna H. Wu, Wendy Brewster, Hoda Anton-Culver, Argyrios Ziogas, Steven A. NarodDouglas A. Levine, Stanley B. Kaye, Robert Brown, Jim Paul, James Flanagan, Weiva Sieh, Valerie McGuire, Alice S. Whittemore, Ian Campbell, Martin E. Gore, Jolanta Lissowska, Hanna P. Yang, Krzysztof Medrek, Jacek Gronwald, Jan Lubinski, Anna Jakubowska, Nhu D. Le, Linda S. Cook, Linda E. Kelemen, Angela Brook-Wilson, Leon F.A.G. Massuger, Lambertus A. Kiemeney, Katja K.H. Aben, Anne M. Van Altena, Richard Houlston, Ian Tomlinson, Rachel T. Palmieri, Patricia G. Moorman, Joellen Schildkraut, Edwin S. Iversen, Catherine Phelan, Robert A. Vierkant, Julie M. Cunningham, Ellen L. Goode, Brooke L. Fridley, Susan Kruger-Kjaer, Jan Blaeker, Estrid Hogdall, Claus Hogdall, Jenny Gross, Beth Y. Karlan, Roberta B. Ness, Robert P. Edwards, Kunle Odunsi, Kirsten B. Moyisch, Julie A. Baker, Francesmary Modugno, Tuomas Heikkinenen, Ralf Butzow, Heli Nevanlinna, Arto Leminen, Natalia Bogdanova, Natalia Antonenkova, Thilo Doerk, Peter Hillemanns, Matthias Dürst, Ingo Runnebaum, Pamela J. Thompson, Michael E. Carney, Marc T. Goodman, Galina Lurie, Shan Wang-Gohrke, Rebecca Hein, Jenny Chang-Claude, Mary Anne Rossing, Kara L. Cushing-Haugen, Jennifer Doherty, Chu Chen, Thorunn Rafnar, Soren Besenbacher, Patrick Sulem, Kari Stefansson, Michael J. Birrer, Kathryn L. Terry, Dena Hernandez, Daniel W. Cramer, Ignace Vergote, Frederic Amant, Diether Lambrechts, Evelyn Despierre, Peter A. Fasching, Matthias W. Beckmann, Falk C. Thiel, Arif B. Ekici, Xiaoqing Chen, Sharon E. Johnatty, Penelope M. Webb, Jonathan Beesley, Stephen Chanock, Montserrat Garcia-Closas, Tom Sellers, Douglas F. Easton, Andrew Berchuck, Georgia Chenevix-Trench, Paul D.P. Pharoah, Simon A. Gayther

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Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5×10^-4 and P = 6×10^-4, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3×10^-9 and P = 4×10^-11, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

Original language	English
Pages (from-to)	880-884
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	10
DOIs	https://doi.org/10.1038/ng.666
State	Published - Oct 2010

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Bolton, K. L., Tyrer, J., Song, H., Ramus, S. J., Notaridou, M., Jones, C., Sher, T., Gentry-Maharaj, A., Wozniak, E., Tsai, Y. Y., Weidhaas, J., Paik, D., Van Den Berg, D. J., Stram, D. O., Pearce, C. L., Wu, A. H., Brewster, W., Anton-Culver, H., Ziogas, A., ... Gayther, S. A. (2010). Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nature Genetics, 42(10), 880-884. https://doi.org/10.1038/ng.666

@article{283616bde65b4c58812dcdc67a4859bc,

title = "Common variants at 19p13 are associated with susceptibility to ovarian cancer",

abstract = "Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5×10-4 and P = 6×10-4, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3×10-9 and P = 4×10-11, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.",

author = "Bolton, {Kelly L.} and Jonathan Tyrer and Honglin Song and Ramus, {Susan J.} and Maria Notaridou and Chris Jones and Tanya Sher and Aleksandra Gentry-Maharaj and Eva Wozniak and Tsai, {Ya Yu} and Joanne Weidhaas and Daniel Paik and {Van Den Berg}, {David J.} and Stram, {Daniel O.} and Pearce, {Celeste Leigh} and Wu, {Anna H.} and Wendy Brewster and Hoda Anton-Culver and Argyrios Ziogas and Narod, {Steven A.} and Levine, {Douglas A.} and Kaye, {Stanley B.} and Robert Brown and Jim Paul and James Flanagan and Weiva Sieh and Valerie McGuire and Whittemore, {Alice S.} and Ian Campbell and Gore, {Martin E.} and Jolanta Lissowska and Yang, {Hanna P.} and Krzysztof Medrek and Jacek Gronwald and Jan Lubinski and Anna Jakubowska and Le, {Nhu D.} and Cook, {Linda S.} and Kelemen, {Linda E.} and Angela Brook-Wilson and Massuger, {Leon F.A.G.} and Kiemeney, {Lambertus A.} and Aben, {Katja K.H.} and {Van Altena}, {Anne M.} and Richard Houlston and Ian Tomlinson and Palmieri, {Rachel T.} and Moorman, {Patricia G.} and Joellen Schildkraut and Iversen, {Edwin S.} and Catherine Phelan and Vierkant, {Robert A.} and Cunningham, {Julie M.} and Goode, {Ellen L.} and Fridley, {Brooke L.} and Susan Kruger-Kjaer and Jan Blaeker and Estrid Hogdall and Claus Hogdall and Jenny Gross and Karlan, {Beth Y.} and Ness, {Roberta B.} and Edwards, {Robert P.} and Kunle Odunsi and Moyisch, {Kirsten B.} and Baker, {Julie A.} and Francesmary Modugno and Tuomas Heikkinenen and Ralf Butzow and Heli Nevanlinna and Arto Leminen and Natalia Bogdanova and Natalia Antonenkova and Thilo Doerk and Peter Hillemanns and Matthias D{\"u}rst and Ingo Runnebaum and Thompson, {Pamela J.} and Carney, {Michael E.} and Goodman, {Marc T.} and Galina Lurie and Shan Wang-Gohrke and Rebecca Hein and Jenny Chang-Claude and Rossing, {Mary Anne} and Cushing-Haugen, {Kara L.} and Jennifer Doherty and Chu Chen and Thorunn Rafnar and Soren Besenbacher and Patrick Sulem and Kari Stefansson and Birrer, {Michael J.} and Terry, {Kathryn L.} and Dena Hernandez and Cramer, {Daniel W.} and Ignace Vergote and Frederic Amant and Diether Lambrechts and Evelyn Despierre and Fasching, {Peter A.} and Beckmann, {Matthias W.} and Thiel, {Falk C.} and Ekici, {Arif B.} and Xiaoqing Chen and Johnatty, {Sharon E.} and Webb, {Penelope M.} and Jonathan Beesley and Stephen Chanock and Montserrat Garcia-Closas and Tom Sellers and Easton, {Douglas F.} and Andrew Berchuck and Georgia Chenevix-Trench and Pharoah, {Paul D.P.} and Gayther, {Simon A.}",

note = "Funding Information: We thank all the individuals who took part in this study and all the researchers, clinicians and administrative staff who have made possible the many studies contributing to this work. In particular we thank A. Ryan and J. Ford (United Kingdom Ovarian Cancer Population Study (UKOPS)); J. Morrison, P. Harrington and the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) team (SEA); U. Eilber and T. Koehler (German Ovarian Cancer Study (GER)); D. Bowtell, A. deFazio, D. Gertig and A. Green (Australian Ovarian Cancer Study (AOCS)); A. Green, P. Parsons, N. Hayward and D. Whiteman (Australian Cancer Study (ACS)); L. Gacucova (Hannover-Minsk Ovarian Cancer Study (HMOCS)); S. Haubold, P. Sch{\"u}rmann, F. Kramer, W. Zheng, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (Hannover-Jena Ovarian Cancer Study (HJOCS)); and L. Brinton, M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M. Stagner (NCI Ovarian Cancer Case-Control Study in Poland (POL2)). The genotyping and data analysis for this study was supported by a project grant from Cancer Research UK. We acknowledge the computational resources provided by the University of Cambridge (CamGrid). This study makes use of data generated by the Wellcome Trust Case-Control consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/. Funding for the project was provided by the Wellcome Trust under award 076113. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of K. Sladek Smith. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute. Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov/. S.J.R. is supported by the Mermaid/Eve Appeal. G.C.-T. and P.M.W. are supported by the National Health and Medical Research Council. P.A.F. is supported by the Deutsche Krebshilfe. M.E.G. acknowledges National Health Service funding to the National Institutes of Health Research Centre at the Royal Marsden Hospital, and D.F.E. is a Principal Research Fellow of Cancer Research UK. Funding of the constituent studies was provided by the Danish Cancer Society, the Ovarian Cancer Research Fund (PPD/RPCI.07), the Roswell Park Cancer Institute Alliance Foundation, the US National Cancer Institute (CA58860, CA92044, P50CA105009, R01CA122443, R01CA126841-01, R01CA16056, R01CA61107, R01CA71766, R01CA054419, R01CA114343, R01CA87538, R01CA112523, R01CA58598, N01CN55424, N01PC35137 and Intramural research funds), the US Army Medical Research and Material Command (DAMD17-01-1-0729), Cancer Council Victoria, Cancer Council Queensland, Cancer Council New South Wales, Cancer Council South Australia, Cancer Council Tasmania and Cancer Foundation of Western Australia, the National Health and Medical Research Council of Australia (199600 and 400281), the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401), the state of Baden-W{\"u}rttemberg through Medical Faculty of the University of Ulm (P.685), the Mayo Foundation, the Lon V. Smith Foundation (LVS-39420), the Oak Foundation, the University College Hospital National Institute for Health Research Biomedical Research Centre and the Royal Marsden Hospital Biomedical Research Centre.",

year = "2010",

month = oct,

doi = "10.1038/ng.666",

language = "English",

volume = "42",

pages = "880--884",

journal = "Nature Genetics",

issn = "1061-4036",

number = "10",

}

Bolton, KL, Tyrer, J, Song, H, Ramus, SJ, Notaridou, M, Jones, C, Sher, T, Gentry-Maharaj, A, Wozniak, E, Tsai, YY, Weidhaas, J, Paik, D, Van Den Berg, DJ, Stram, DO, Pearce, CL, Wu, AH, Brewster, W, Anton-Culver, H, Ziogas, A, Narod, SA, Levine, DA, Kaye, SB, Brown, R, Paul, J, Flanagan, J, Sieh, W, McGuire, V, Whittemore, AS, Campbell, I, Gore, ME, Lissowska, J, Yang, HP, Medrek, K, Gronwald, J, Lubinski, J, Jakubowska, A, Le, ND, Cook, LS, Kelemen, LE, Brook-Wilson, A, Massuger, LFAG, Kiemeney, LA, Aben, KKH, Van Altena, AM, Houlston, R, Tomlinson, I, Palmieri, RT, Moorman, PG, Schildkraut, J, Iversen, ES, Phelan, C, Vierkant, RA, Cunningham, JM, Goode, EL, Fridley, BL, Kruger-Kjaer, S, Blaeker, J, Hogdall, E, Hogdall, C, Gross, J, Karlan, BY, Ness, RB, Edwards, RP, Odunsi, K, Moyisch, KB, Baker, JA, Modugno, F, Heikkinenen, T, Butzow, R, Nevanlinna, H, Leminen, A, Bogdanova, N, Antonenkova, N, Doerk, T, Hillemanns, P, Dürst, M, Runnebaum, I, Thompson, PJ, Carney, ME, Goodman, MT, Lurie, G, Wang-Gohrke, S, Hein, R, Chang-Claude, J, Rossing, MA, Cushing-Haugen, KL, Doherty, J, Chen, C, Rafnar, T, Besenbacher, S, Sulem, P, Stefansson, K, Birrer, MJ, Terry, KL, Hernandez, D, Cramer, DW, Vergote, I, Amant, F, Lambrechts, D, Despierre, E, Fasching, PA, Beckmann, MW, Thiel, FC, Ekici, AB, Chen, X, Johnatty, SE, Webb, PM, Beesley, J, Chanock, S, Garcia-Closas, M, Sellers, T, Easton, DF, Berchuck, A, Chenevix-Trench, G, Pharoah, PDP & Gayther, SA 2010, 'Common variants at 19p13 are associated with susceptibility to ovarian cancer', Nature Genetics, vol. 42, no. 10, pp. 880-884. https://doi.org/10.1038/ng.666

TY - JOUR

T1 - Common variants at 19p13 are associated with susceptibility to ovarian cancer

AU - Bolton, Kelly L.

AU - Tyrer, Jonathan

AU - Song, Honglin

AU - Ramus, Susan J.

AU - Notaridou, Maria

AU - Jones, Chris

AU - Sher, Tanya

AU - Gentry-Maharaj, Aleksandra

AU - Wozniak, Eva

AU - Tsai, Ya Yu

AU - Weidhaas, Joanne

AU - Paik, Daniel

AU - Van Den Berg, David J.

AU - Stram, Daniel O.

AU - Pearce, Celeste Leigh

AU - Wu, Anna H.

AU - Brewster, Wendy

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Narod, Steven A.

AU - Levine, Douglas A.

AU - Kaye, Stanley B.

AU - Brown, Robert

AU - Paul, Jim

AU - Flanagan, James

AU - Sieh, Weiva

AU - McGuire, Valerie

AU - Whittemore, Alice S.

AU - Campbell, Ian

AU - Gore, Martin E.

AU - Lissowska, Jolanta

AU - Yang, Hanna P.

AU - Medrek, Krzysztof

AU - Gronwald, Jacek

AU - Lubinski, Jan

AU - Jakubowska, Anna

AU - Le, Nhu D.

AU - Cook, Linda S.

AU - Kelemen, Linda E.

AU - Brook-Wilson, Angela

AU - Massuger, Leon F.A.G.

AU - Kiemeney, Lambertus A.

AU - Aben, Katja K.H.

AU - Van Altena, Anne M.

AU - Houlston, Richard

AU - Tomlinson, Ian

AU - Palmieri, Rachel T.

AU - Moorman, Patricia G.

AU - Schildkraut, Joellen

AU - Iversen, Edwin S.

AU - Phelan, Catherine

AU - Vierkant, Robert A.

AU - Cunningham, Julie M.

AU - Goode, Ellen L.

AU - Fridley, Brooke L.

AU - Kruger-Kjaer, Susan

AU - Blaeker, Jan

AU - Hogdall, Estrid

AU - Hogdall, Claus

AU - Gross, Jenny

AU - Karlan, Beth Y.

AU - Ness, Roberta B.

AU - Edwards, Robert P.

AU - Odunsi, Kunle

AU - Moyisch, Kirsten B.

AU - Baker, Julie A.

AU - Modugno, Francesmary

AU - Heikkinenen, Tuomas

AU - Butzow, Ralf

AU - Nevanlinna, Heli

AU - Leminen, Arto

AU - Bogdanova, Natalia

AU - Antonenkova, Natalia

AU - Doerk, Thilo

AU - Hillemanns, Peter

AU - Dürst, Matthias

AU - Runnebaum, Ingo

AU - Thompson, Pamela J.

AU - Carney, Michael E.

AU - Goodman, Marc T.

AU - Lurie, Galina

AU - Wang-Gohrke, Shan

AU - Hein, Rebecca

AU - Chang-Claude, Jenny

AU - Rossing, Mary Anne

AU - Cushing-Haugen, Kara L.

AU - Doherty, Jennifer

AU - Chen, Chu

AU - Rafnar, Thorunn

AU - Besenbacher, Soren

AU - Sulem, Patrick

AU - Stefansson, Kari

AU - Birrer, Michael J.

AU - Terry, Kathryn L.

AU - Hernandez, Dena

AU - Cramer, Daniel W.

AU - Vergote, Ignace

AU - Amant, Frederic

AU - Lambrechts, Diether

AU - Despierre, Evelyn

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Thiel, Falk C.

AU - Ekici, Arif B.

AU - Chen, Xiaoqing

AU - Johnatty, Sharon E.

AU - Webb, Penelope M.

AU - Beesley, Jonathan

AU - Chanock, Stephen

AU - Garcia-Closas, Montserrat

AU - Sellers, Tom

AU - Easton, Douglas F.

AU - Berchuck, Andrew

AU - Chenevix-Trench, Georgia

AU - Pharoah, Paul D.P.

AU - Gayther, Simon A.

N1 - Funding Information: We thank all the individuals who took part in this study and all the researchers, clinicians and administrative staff who have made possible the many studies contributing to this work. In particular we thank A. Ryan and J. Ford (United Kingdom Ovarian Cancer Population Study (UKOPS)); J. Morrison, P. Harrington and the Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH) team (SEA); U. Eilber and T. Koehler (German Ovarian Cancer Study (GER)); D. Bowtell, A. deFazio, D. Gertig and A. Green (Australian Ovarian Cancer Study (AOCS)); A. Green, P. Parsons, N. Hayward and D. Whiteman (Australian Cancer Study (ACS)); L. Gacucova (Hannover-Minsk Ovarian Cancer Study (HMOCS)); S. Haubold, P. Schürmann, F. Kramer, W. Zheng, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (Hannover-Jena Ovarian Cancer Study (HJOCS)); and L. Brinton, M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M. Stagner (NCI Ovarian Cancer Case-Control Study in Poland (POL2)). The genotyping and data analysis for this study was supported by a project grant from Cancer Research UK. We acknowledge the computational resources provided by the University of Cambridge (CamGrid). This study makes use of data generated by the Wellcome Trust Case-Control consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/. Funding for the project was provided by the Wellcome Trust under award 076113. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of K. Sladek Smith. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute. Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov/. S.J.R. is supported by the Mermaid/Eve Appeal. G.C.-T. and P.M.W. are supported by the National Health and Medical Research Council. P.A.F. is supported by the Deutsche Krebshilfe. M.E.G. acknowledges National Health Service funding to the National Institutes of Health Research Centre at the Royal Marsden Hospital, and D.F.E. is a Principal Research Fellow of Cancer Research UK. Funding of the constituent studies was provided by the Danish Cancer Society, the Ovarian Cancer Research Fund (PPD/RPCI.07), the Roswell Park Cancer Institute Alliance Foundation, the US National Cancer Institute (CA58860, CA92044, P50CA105009, R01CA122443, R01CA126841-01, R01CA16056, R01CA61107, R01CA71766, R01CA054419, R01CA114343, R01CA87538, R01CA112523, R01CA58598, N01CN55424, N01PC35137 and Intramural research funds), the US Army Medical Research and Material Command (DAMD17-01-1-0729), Cancer Council Victoria, Cancer Council Queensland, Cancer Council New South Wales, Cancer Council South Australia, Cancer Council Tasmania and Cancer Foundation of Western Australia, the National Health and Medical Research Council of Australia (199600 and 400281), the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401), the state of Baden-Württemberg through Medical Faculty of the University of Ulm (P.685), the Mayo Foundation, the Lon V. Smith Foundation (LVS-39420), the Oak Foundation, the University College Hospital National Institute for Health Research Biomedical Research Centre and the Royal Marsden Hospital Biomedical Research Centre.

PY - 2010/10

Y1 - 2010/10

N2 - Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5×10-4 and P = 6×10-4, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3×10-9 and P = 4×10-11, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

AB - Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.11, rs8170 and rs2363956, showed evidence of association with survival (overall P = 5×10-4 and P = 6×10-4, respectively), but they did not replicate in phase 3. However, the same two SNPs demonstrated genome-wide significance for risk of serous EOC (P = 3×10-9 and P = 4×10-11, respectively). Expression analysis of candidate genes at this locus in ovarian tumors supported a role for the BRCA1-interacting gene C19orf62, also known as MERIT40, which contains rs8170, in EOC development.

UR - http://www.scopus.com/inward/record.url?scp=77957584092&partnerID=8YFLogxK

U2 - 10.1038/ng.666

DO - 10.1038/ng.666

M3 - Article

C2 - 20852633

AN - SCOPUS:77957584092

SN - 1061-4036

VL - 42

SP - 880

EP - 884

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

Common variants at 19p13 are associated with susceptibility to ovarian cancer

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