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Fertil Steril. 2016 Jan;105(1):35-43.e1-10. doi: 10.1016/j.fertnstert.2015.09.023. Epub 2015 Oct 23.

Evidence of a genetic link between endometriosis and ovarian cancer.

Collaborators (131)

Ness RB, Dansonka-Mieszkowska A, Gentry-Maharaj A, Hein A, Whittemore AS, Jensen A, du Bois A, Brooks-Wilson A, Rudolph A, Jakubowska A, Wu AH, Ziogas A, Ekici AB, Leminen A, Rosen B, Spiewankiewicz B, Karlan BY, Trabert B, Fridley BL, Gilks CB, Krakstad C, Phelan CM, Cybulski C, Walsh C, Hogdall C, Cramer DW, Huntsman DG, Eccles D, Lambrechts D, Liang D, Levine DA, Iversen ES, Bandera EV, Poole EM, Goode EL, Van Nieuwenhuysen E, Hogdall E, Bruinsma F, Heitz F, Modugno F, Giles GG, Risch HA, Baker H, Salvesen HB, Nevanlinna H, Anton-Culver H, Song H, McNeish I, Campbell IG, Vergote I, Runnebaum IB, Tangen IL, Schwaab I, Gronwald J, Paul J, Lubinski J, Doherty JA, Chang-Claude J, Lester J, Schildkraut JM, McLaughlin JR, Lissowska J, Kupryjanczyk J, Tyrer J, Kelley JL, Rothstein JH, Cunningham JM, Lu K, Carty K, Terry KL, Aben KK, Moysich KB, Wicklund KG, Odunsi K, Kiemeney LA, Sucheston-Campbell L, Lundvall L, Massuger LF, Pelttari LM, Kelemen LE, Cook LS, Bjorge L, Nedergaard L, Brinton LA, Wilkens LR, Pike MC, Goodman MT, Bisogna M, Rossing MA, Beckmann MW, Dürst M, Southey MC, Kellar M, Hildebrandt MA, Siddiqui N, Antonenkova N, Bogdanova N, Le ND, Wentzensen N, Thompson PJ, Harrington P, Webb PM, Fasching PA, Hillemanns P, Harter P, Sobiczewski P, Weber RP, Butzow R, Edwards RP, Vierkant RA, Glasspool R, Orsulic S, Lambrechts S, Olson SH, Wang-Gohrke S, Lele S, Tworoger SS, Gayther SA, Missmer SA, Narod SA, Ramus SJ, Kjaer SK, Pejovic T, Dörk T, Eilber U, Menon U, McGuire V, Sieh W, Wu X, Bean Y, Shvetsov YB.

Author information

1
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
2
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California.
3
Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
4
Department of Oncology and Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom.
5
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
6
Department of Oncology and Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom; Department of Public Health and Primary Care and Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom.
7
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan. Electronic address: lpearce@umich.edu.

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.

KEYWORDS:

Endometriosis; SNPs; genetic variation; ovarian cancer

PMID:
26477498
PMCID:
PMC5068352
DOI:
10.1016/j.fertnstert.2015.09.023
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Statement Dr. Pharoah reports grants from National Institutes of Health and Cancer Research UK during the conduct of the study.

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