Abstract
Objective To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. Design Pooled genetic analysis. Setting University hospital. Patient(s) Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. Intervention(s) None. Main Outcome Measure(s) Endometriosis-associated genetic variation and ovarian cancer. Result(s) There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. Conclusion(s) By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.
| Original language | English |
|---|---|
| Pages (from-to) | 35-43.e10 |
| Journal | Fertility and Sterility |
| Volume | 105 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2016 |
Keywords
- Endometriosis
- SNPs
- genetic variation
- ovarian cancer
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In: Fertility and Sterility, Vol. 105, No. 1, 2016, p. 35-43.e10.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Evidence of a genetic link between endometriosis and ovarian cancer
AU - Ovarian Cancer Association Consortium
AU - Australian Cancer Study (Ovarian Cancer)
AU - Australian ovarian cancer study group
AU - Lee, Alice W.
AU - Templeman, Claire
AU - Stram, Douglas A.
AU - Beesley, Jonathan
AU - Tyrer, Jonathan
AU - Berchuck, Andrew
AU - Pharoah, Paul P.
AU - Chenevix-Trench, Georgia
AU - Pearce, Celeste Leigh
AU - Ness, Roberta B.
AU - Dansonka-Mieszkowska, Agnieszka
AU - Gentry-Maharaj, Aleksandra
AU - Hein, Alexander
AU - Whittemore, Alice S.
AU - Jensen, Allan
AU - Du Bois, Andreas
AU - Brooks-Wilson, Angela
AU - Rudolph, Anja
AU - Jakubowska, Anna
AU - Wu, Anna H.
AU - Ziogas, Argyrios
AU - Ekici, Arif B.
AU - Leminen, Arto
AU - Rosen, Barry
AU - Spiewankiewicz, Beata
AU - Karlan, Beth Y.
AU - Trabert, Britton
AU - Fridley, Brooke L.
AU - Gilks, C. Blake
AU - Krakstad, Camilla
AU - Phelan, Catherine M.
AU - Cybulski, Cezary
AU - Walsh, Christine
AU - Hogdall, Claus
AU - Cramer, Daniel W.
AU - Huntsman, David G.
AU - Eccles, Diana
AU - Lambrechts, Diether
AU - Liang, Dong
AU - Levine, Douglas A.
AU - Iversen, Edwin S.
AU - Bandera, Elisa V.
AU - Poole, Elizabeth M.
AU - Goode, Ellen L.
AU - Van Nieuwenhuysen, Els
AU - Hogdall, Estrid
AU - Bruinsma, Fiona
AU - Heitz, Florian
AU - Rothstein, Joseph H.
AU - Sieh, Weiva
N1 - Funding Information: This work was supported by the National Cancer Institute ( K07-CA095666 , K07-CA80668 , K07-CA143047 , K22-CA138563 , N01-CN55424 , N01-PC67001 , N01-PC067010 , N01-PC035137 , P01-CA017054 , P01-CA087696 , P30-CA072720 , P30-CA15083 , P30-CA008748 , P50-CA159981 , P50-CA105009 , P50-CA136393 , R01-CA149429 , R01-CA014089 , R01-CA016056 , R01-CA017054 , R01-CA049449 , R01-CA050385 , R01-CA054419 , R01-CA058598 , R01-CA058860 , R01-CA061107 , R01-CA061132 , R01-CA063678 , R01-CA063682 , R01-CA067262 , R01-CA071766 , R01-CA074850 , R01-CA076016 , R01-CA080978 , R01-CA083918 , R01-CA087538 , R01-CA092044 , R01-CA095023 , R01-CA122443 , R01-CA112523 , R01-CA114343 , R01-CA126841 , R01-CA136924 , R03-CA113148 , R03-CA115195 , U01-CA069417 , U01-CA071966 , and Intramural research funds); the European Commission's Seventh Framework Programme (agreement number 223175 HEALTH F2 2009-223175); a National Cancer Institute, Cancer Post-GWAS Initiative (U19-CA148112); the Genetic Associations and Mechanisms in Oncology (GAME-ON); the Ovarian Cancer Research Fund (thanks to donations by the family and friends of Kathryn Sladek Smith) (PPD/RPCI.07); the National Institute of Environmental Health Sciences ( T32ES013678 to A.W.L.); National Health and Medical Research Council (to G.-C.T.); American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN to B.K.); National Center for Advancing Translational Sciences (NCATS) ( UL1TR000124 to B.K.); California Cancer Research Program (00-01389V-20170, N01-CN25403, 2II0200); the Canadian Institutes of Health Research ( MOP-86727 ); Cancer Australia; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124); the Danish Cancer Society ( 94-222-52 ); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; the L & S Milken Foundation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); the Roswell Park Cancer Institute Alliance Foundation; the National Institutes of Health/National Center for Research Resources/General Clinical Research Center ( MO1-RR000056 ); the US Army Medical Research and Material Command ( DAMD17-01-1-0729 , DAMD17-02-1-0666 , DAMD17-02-1-0669 , W81XWH-07-0449 , W81XWH-10-1-02802 ); the U.S. Public Health Service ( PSA-042205 ); the National Health and Medical Research Council of Australia ( 199600 , 400281 ); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the State of Baden-Wurttemberg through Medical Faculty of the University of Ulm ( P.685 ); the German Cancer Research Center; the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the Oregon Health & Science University Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital “Womens Health Theme” and the Royal Marsden Hospital; and WorkSafeBC 14. Funding Information: This work was supported by the National Cancer Institute (K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC67001, N01PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA072720, P30-CA15083, P30-CA008748, P50-CA159981, P50-CA105009, P50-CA136393, R01-CA149429, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01-CA058598, R01-CA058860, R01CA061107, R01-CA061132, R01-CA063678, R01-CA063682, R01-CA067262, R01-CA071766, R01-CA074850, R01-CA076016, R01-CA080978, R01CA083918, R01-CA087538, R01-CA092044, R01-CA095023, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01-CA136924, R03CA113148, R03-CA115195, U01-CA069417, U01-CA071966, and Intramural research funds); the European Commission''s Seventh Framework Programme (agreement number 22317 5HEALTHF 22009-223175);a National Cancer Institute, Cancer Post - GWAS Initiative (U19-CA148112); the Genetic Associations and Mechanisms in Oncology (GAME-ON); the Ovarian Cancer Research Fund (thanks to donations by the family and friends of Kathryn Sladek Smith) (PPD/RPCI.07); the National Institute of Environmental Health Sciences (T32ES013678 to A.W.L.); National Health and Medical Research Council (to G.-C.T.); American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN to B.K.); National Center for Advancing Translational Sciences(NCATS)(UL1TR000124 to B.K.); California Cancer Research Program (00-01389V-20170, N01-CN25403,2II0200);the Canadian Institutes of Health Research (MOP-86727); Cancer Australia; Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124); the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; the L&SMilken Foundation; the Polish Ministry of Science and Higher Education (4 PO5C02814, 2 PO5A 06827); the Roswell Park Cancer Institute Alliance Foundation; the National Institutes of Health/National Centerfor Research Resources/General Clinical Research Center (MO1-RR000056); the US Army Medical Research and Material Command (DAMD17-01-1-0729, DAMD1702-1-0666, DAMD17-02-1-0669, W81XWH-07-0449, W81XWH-10-1-02802);the U.S. Public Health Service(PSA-042205); theNational Health andMedical Research Council of Australia (199600, 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the State of Baden-Wurttemberg through Medical Faculty of the University of Ulm (P.685); the German Cancer Research Center; the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the Oregon Health&Science University Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital "Womens Health Theme" and the Royal Marsden Hospital; and Work SafeBC 14. Ovarian Cancer Association Consortium: Roberta B. Ness, Agnieszka Dansonka-Mieszkowska, Aleksandra Gentry-Maharaj, Alexander Hein, Alice S. Whittemore, Allan Jensen, Andreas du Bois, Angela Brooks-Wilson, Anja Rudolph, Anna Jakubowska, Anna H. Wu, Argyrios Ziogas, Arif B. Ekici, Arto Leminen, Australian Cancer Study (Ovarian Cancer), Australian Ovarian Cancer Study Group, Barry Rosen, Beata Spiewankiewicz, Beth Y. Karlan, Britton Trabert, Brooke L. Fridley, C. Blake Gilks, Camilla Krakstad, Catherine M. Phelan, Cezary Cybulski, Christine Walsh, Claus Hogdall, Daniel W. Cramer, David G. Huntsman, Diana Eccles, Diether Lambrechts, Dong Liang, Douglas A. Levine, Edwin S. Iversen, Elisa V. Bandera, Elizabeth M. Poole, Ellen L. Goode, Els Van Nieuwenhuysen, Estrid Hogdall, Fiona Bruinsma, Florian Heitz, Francesmary Modugno, Graham G. Giles, Harvey A. Risch, Helen Baker, Helga B. Salvesen, Heli Nevanlinna, Hoda Anton-Culver, Honglin Song, Iain McNeish, Ian G. Campbell, Ignace Vergote, Ingo B. Runnebaum, Ingvild L. Tangen, Ira Schwaab, Jacek Gronwald, James Paul, Jan Lubinski, Jennifer A. Doherty, Jenny Chang-Claude, Jenny Lester, Joellen M. Schildkraut, John R. McLaughlin, Jolanta Lissowska, Jolanta Kupryjanczyk, Jonathan Tyrer, Joseph L. Kelley, Joseph H. Rothstein, Julie M. Cunningham, Karen Lu, Karen Carty, Kathryn L. Terry, Katja K.H. Aben, Kirsten B. Moysich, Kristine G. Wicklund, Kunle Odunsi, Lambertus A. Kiemeney, Lara Sucheston-Campbell, Lene Lundvall, Leon F.A.G. Massuger, Liisa M. Pelttari, Linda E. Kelemen, Linda S. Cook, Line Bjorge, Lotte Nedergaard, Louise A. Brinton, Lynne R. Wilkens, Malcolm C. Pike, Marc T. Goodman, Maria Bisogna, Mary Anne Rossing, Matthias W. Beckmann, Matthias Dürst, Melissa C. Southey, Melissa Kellar, Michelle A.T. Hildebrandt, Nadeem Siddiqui, Natalia Antonenkova, Natalia Bogdanova, Nhu D. Le, Nicolas Wentzensen, Pamela J. Thompson, Patricia Harrington, Penelope M. Webb, Peter A. Fasching, Peter Hillemanns, Philipp Harter, Piotr Sobiczewski, Rachel Palmieri Weber, Ralf Butzow, Robert P. Edwards, Robert A. Vierkant, Rosalind Glasspool, Sandra Orsulic, Sandrina Lambrechts, Sara H. Olson, Shan Wang-Gohrke, Shashi Lele, Shelley S. Tworoger, Simon A. Gayther, Stacey A. Missmer, Steven A. Narod, Susan J. Ramus, Susanne K. Kjaer, Tanja Pejovic, Thilo Dörk, Ursula Eilber, Usha Menon, Valerie McGuire, Weiva Sieh, Xifeng Wu, Yukie Bean, Yurii B Shvetsov. The authors thank all the individuals who took part in this study and all the researchers, clinicians, and technical and administrative staff who have made possible the many studies contributing to this work. In particular, the authors thank D. Bowtell, A. deFazio, D. Gertig, A. Green, P. Parsons, N. Hayward, and D. Whiteman (AUS) (see Supplemental Table 1 for site abbreviations); G. Peuteman, T. Van Brussel, and D. Smeets (BEL); the staff of the genotyping unit, S. LaBoissiere and F. Robidoux (Genome Quebec); L. Gacucova (HMO); P. Schurmann, F. Kramer, W. Zheng, T. W. Park, Simon, K. Beer-Grondke, and D. Schmidt (HJO); S. Windebank, C. Hilker, and J. Vollenweider (MAY); the state cancer registries of AL, AZ, AR, CA, CO, CT, DE, FL, GA, HI, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WYL (NHS); L. Paddock, M. King, L. Rodriguez-Rodriguez, A. Samoila, and Y. Bensman (NJO); M. Sherman, A. Hutchinson, N. Szeszenia-Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao, and M. Stagner (POL); C. Luccarini, P. Harrington the SEARCH team and ECRIC (SEA); I. Jacobs, M. Widschwendter, E. Wozniak, N. Balogun, A. Ryan, C. Karpinskyj, and J. Ford (UKO); Carole Pye (UKR); A. Amin Al Olama, J. Dennis, E. Dicks, K. Michilaidou, K. Kuchenbaker (COGS); and G. Montgomery. Funding Information: P.P.P. reports grants from the National Institutes of Health and Cancer Research UK during the conduct of the study. A.W.L. has nothing to disclose. C.T. has nothing to disclose. D.A.S. has nothing to disclose. J.B. has nothing to disclose. J.T. has nothing to disclose. A.B. has nothing to disclose. G.C.-T. has nothing to disclose. C.L.P. has nothing to disclose.
PY - 2016
Y1 - 2016
N2 - Objective To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. Design Pooled genetic analysis. Setting University hospital. Patient(s) Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. Intervention(s) None. Main Outcome Measure(s) Endometriosis-associated genetic variation and ovarian cancer. Result(s) There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. Conclusion(s) By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.
AB - Objective To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. Design Pooled genetic analysis. Setting University hospital. Patient(s) Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. Intervention(s) None. Main Outcome Measure(s) Endometriosis-associated genetic variation and ovarian cancer. Result(s) There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. Conclusion(s) By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.
KW - Endometriosis
KW - SNPs
KW - genetic variation
KW - ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=84949239375&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2015.09.023
DO - 10.1016/j.fertnstert.2015.09.023
M3 - Article
C2 - 26477498
AN - SCOPUS:84949239375
SN - 0015-0282
VL - 105
SP - 35-43.e10
JO - Fertility and Sterility
JF - Fertility and Sterility
IS - 1
ER -