Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Lu, Yi, Cuellar-Partida, Gabriel, Painter, Jodie N., Nyholt, Dale R., Morris, Andrew P., Fasching, Peter A., Hein, Alexander, Burghaus, Stefanie, Beckmann, Matthias W., Lambrechts, Diether, Van Nieuwenhuysen, Els, Vergote, Ignace, Vanderstichele, Adriaan, Doherty, Jennifer Anne, Rossing, Mary Anne, Wicklund, Kristine G., Chang-Claude, Jenny, Eilber, Ursula, Rudolph, Anja, Wang-Gohrke, Shan, Goodman, Marc T., Bogdanova, Natalia, Doerk, Thilo, Duerst, Matthias, Hillemanns, Peter, Runnebaum, Ingo B., Antonenkova, Natalia, Butzow, Ralf, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M., Edwards, Robert P., Kelley, Joseph L., Modugno, Francesmary, Moysich, Kirsten B., Ness, Roberta B., Cannioto, Rikki, Hogdall, Estrid, Jensen, Allan, Giles, Graham G., Bruinsma, Fiona, Kjaer, Susanne K., Hildebrandt, Michelle A. T., Liang, Dong, Lu, Karen H., Wu, Xifeng, Bisogna, Maria, Dao, Fanny, Levine, Douglas A., Cramer, Daniel W., Terry, Kathryn L., Tworoger, Shelley S., Missmer, Stacey, Bjorge, Line, Salvesen, Helga B., Kopperud, Reidun K., Bischof, Katharina, Aben, Katja K. H., Kiemeney, Lambertus A., Massuger, Leon F. A. G., Brooks-Wilson, Angela, Olson, Sara H., McGuire, Valerie, Rothstein, Joseph H., Sieh, Weiva, Whittemore, Alice S., Cook, Linda S., Le, Nhu D., Gilks, C. Blake, Gronwald, Jacek, Jakubowska, Anna, Lubinski, Jan, Gawelko, Jan, Song, Honglin, Tyrer, Jonathan P., Wentzensen, Nicolas, Brinton, Louise, Trabert, Britton, Lissowska, Jolanta, Mclaughlin, John R., Narod, Steven A., Phelan, Catherine, Anton-Culver, Hoda, Ziogas, Argyrios, Eccles, Diana, Gayther, Simon A., Gentry-Maharaj, Aleksandra, Menon, Usha, Ramus, Susan J., Wu, Anna H., Dansonka-Mieszkowska, Agnieszka, Kupryjanczyk, Jolanta, Timorek, Agnieszka, Szafron, Lukasz, Cunningham, Julie M., Fridley, Brooke L., Winham, Stacey J., Bandera, Elisa V., Poole, Elizabeth M., Morgan, Terry K., Risch, Harvey A., Goode, Ellen L., Schildkraut, Joellen M., Webb, Penelope M., Pearce, Celeste L., Berchuck, Andrew, Pharoah, Paul D. P., Montgomery, Grant W., Zondervan, Krina T., Chenevix-Trench, Georgia and MacGregor, Stuart (2015) Shared genetics underlying epidemiological association between endometriosis and ovarian cancer. Human Molecular Genetics, 24 20: 5955-5964. doi:10.1093/hmg/ddv306

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Author Lu, Yi
Cuellar-Partida, Gabriel
Painter, Jodie N.
Nyholt, Dale R.
Morris, Andrew P.
Fasching, Peter A.
Hein, Alexander
Burghaus, Stefanie
Beckmann, Matthias W.
Lambrechts, Diether
Van Nieuwenhuysen, Els
Vergote, Ignace
Vanderstichele, Adriaan
Doherty, Jennifer Anne
Rossing, Mary Anne
Wicklund, Kristine G.
Chang-Claude, Jenny
Eilber, Ursula
Rudolph, Anja
Wang-Gohrke, Shan
Goodman, Marc T.
Bogdanova, Natalia
Doerk, Thilo
Duerst, Matthias
Hillemanns, Peter
Runnebaum, Ingo B.
Antonenkova, Natalia
Butzow, Ralf
Leminen, Arto
Nevanlinna, Heli
Pelttari, Liisa M.
Edwards, Robert P.
Kelley, Joseph L.
Modugno, Francesmary
Moysich, Kirsten B.
Ness, Roberta B.
Cannioto, Rikki
Hogdall, Estrid
Jensen, Allan
Giles, Graham G.
Bruinsma, Fiona
Kjaer, Susanne K.
Hildebrandt, Michelle A. T.
Liang, Dong
Lu, Karen H.
Wu, Xifeng
Bisogna, Maria
Dao, Fanny
Levine, Douglas A.
Cramer, Daniel W.
Terry, Kathryn L.
Tworoger, Shelley S.
Missmer, Stacey
Bjorge, Line
Salvesen, Helga B.
Kopperud, Reidun K.
Bischof, Katharina
Aben, Katja K. H.
Kiemeney, Lambertus A.
Massuger, Leon F. A. G.
Brooks-Wilson, Angela
Olson, Sara H.
McGuire, Valerie
Rothstein, Joseph H.
Sieh, Weiva
Whittemore, Alice S.
Cook, Linda S.
Le, Nhu D.
Gilks, C. Blake
Gronwald, Jacek
Jakubowska, Anna
Lubinski, Jan
Gawelko, Jan
Song, Honglin
Tyrer, Jonathan P.
Wentzensen, Nicolas
Brinton, Louise
Trabert, Britton
Lissowska, Jolanta
Mclaughlin, John R.
Narod, Steven A.
Phelan, Catherine
Anton-Culver, Hoda
Ziogas, Argyrios
Eccles, Diana
Gayther, Simon A.
Gentry-Maharaj, Aleksandra
Menon, Usha
Ramus, Susan J.
Wu, Anna H.
Dansonka-Mieszkowska, Agnieszka
Kupryjanczyk, Jolanta
Timorek, Agnieszka
Szafron, Lukasz
Cunningham, Julie M.
Fridley, Brooke L.
Winham, Stacey J.
Bandera, Elisa V.
Poole, Elizabeth M.
Morgan, Terry K.
Risch, Harvey A.
Goode, Ellen L.
Schildkraut, Joellen M.
Webb, Penelope M.
Pearce, Celeste L.
Berchuck, Andrew
Pharoah, Paul D. P.
Montgomery, Grant W.
Zondervan, Krina T.
Chenevix-Trench, Georgia
MacGregor, Stuart
Title Shared genetics underlying epidemiological association between endometriosis and ovarian cancer
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 1460-2083
0964-6906
Publication date 2015-06-05
Year available 2015
Sub-type Article (original research)
DOI 10.1093/hmg/ddv306
Open Access Status Not Open Access
Volume 24
Issue 20
Start page 5955
End page 5964
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 1312 Molecular Biology
1311 Genetics
2716 Genetics (clinical)
Abstract Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
Formatted abstract
Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18–0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07–0.89 and 0.40, 95% CI = 0.05–0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11–0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
Keyword Biochemistry & Molecular Biology
Genetics & Heredity
Biochemistry & Molecular Biology
Genetics & Heredity
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID WEWC140014
WT084766/Z/08/Z
241944
223175 HEALTH F2 2009-223175
U19-CA148112
PPD/RPCI.07
00-01389V-20170
MOP-86727
C490/A6187
94-222-52
4 PO5C 028 14
K07-CA095666
MO1-RR000056
DAMD17-01-1-0729
PSA-042205
199600
01GB 9401
P. 685
LVS-39420
339462
FT0991022
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Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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Created: Tue, 12 Apr 2016, 01:44:04 EST by Matthew Lamb on behalf of School of Medicine