Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Yi Lu; Gabriel Cuellar-Partida; Jodie N Painter; Dale R Nyholt; Andrew P Morris; Peter A Fasching; Alexander Hein; Stefanie Burghaus; Matthias W Beckmann; Diether Lambrechts; Els Van Nieuwenhuysen; Ignace Vergote; Adriaan Vanderstichele; Jennifer Anne Doherty; Mary Anne Rossing; Kristine G Wicklund; Jenny Chang-Claude; Ursula Eilber; Anja Rudolph; Shan Wang-Gohrke; Marc T Goodman; Natalia Bogdanova; Thilo Dörk; Matthias Dürst; Peter Hillemanns; Ingo B Runnebaum; Natalia Antonenkova; Ralf Butzow; Arto Leminen; Heli Nevanlinna; Liisa M Pelttari; Robert P Edwards; Joseph L Kelley; Francesmary Modugno; Kirsten B Moysich; Roberta B Ness; Rikki Cannioto; Estrid Høgdall; Allan Jensen; Graham G Giles; Fiona Bruinsma; Susanne K Kjaer; Michelle A T Hildebrandt; Dong Liang; Karen H Lu; Xifeng Wu; Maria Bisogna; Fanny Dao; Douglas A Levine; Daniel W Cramer; Australian Ovarian Cancer Study

doi:10.1093/hmg/ddv306

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Yi Lu, Gabriel Cuellar-Partida, Jodie N Painter, Dale R Nyholt, Andrew P Morris, Peter A Fasching, Alexander Hein, Stefanie Burghaus, Matthias W Beckmann, Diether Lambrechts, Els Van Nieuwenhuysen, Ignace Vergote, Adriaan Vanderstichele, Jennifer Anne Doherty, Mary Anne Rossing, Kristine G Wicklund, Jenny Chang-Claude, Ursula Eilber, Anja Rudolph, Shan Wang-GohrkeMarc T Goodman, Natalia Bogdanova, Thilo Dörk, Matthias Dürst, Peter Hillemanns, Ingo B Runnebaum, Natalia Antonenkova, Ralf Butzow, Arto Leminen, Heli Nevanlinna, Liisa M Pelttari, Robert P Edwards, Joseph L Kelley, Francesmary Modugno, Kirsten B Moysich, Roberta B Ness, Rikki Cannioto, Estrid Høgdall, Allan Jensen, Graham G Giles, Fiona Bruinsma, Susanne K Kjaer, Michelle A T Hildebrandt, Dong Liang, Karen H Lu, Xifeng Wu, Maria Bisogna, Fanny Dao, Douglas A Levine, Daniel W Cramer, Australian Ovarian Cancer Study

Institut for Klinisk Medicin

40 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Human Molecular Genetics
Vol/bind	24
Udgave nummer	20
Sider (fra-til)	5955-64
Antal sider	10
ISSN	0964-6906
DOI	https://doi.org/10.1093/hmg/ddv306
Status	Udgivet - 5 jun. 2015

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10.1093/hmg/ddv306

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Lu, Y., Cuellar-Partida, G., Painter, J. N., Nyholt, D. R., Morris, A. P., Fasching, P. A., Hein, A., Burghaus, S., Beckmann, M. W., Lambrechts, D., Van Nieuwenhuysen, E., Vergote, I., Vanderstichele, A., Doherty, J. A., Rossing, M. A., Wicklund, K. G., Chang-Claude, J., Eilber, U., Rudolph, A., ... Australian Ovarian Cancer Study (2015). Shared genetics underlying epidemiological association between endometriosis and ovarian cancer. Human Molecular Genetics, 24(20), 5955-64. https://doi.org/10.1093/hmg/ddv306

Lu, Y, Cuellar-Partida, G, Painter, JN, Nyholt, DR, Morris, AP, Fasching, PA, Hein, A, Burghaus, S, Beckmann, MW, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I, Vanderstichele, A, Doherty, JA, Rossing, MA, Wicklund, KG, Chang-Claude, J, Eilber, U, Rudolph, A, Wang-Gohrke, S, Goodman, MT, Bogdanova, N, Dörk, T, Dürst, M, Hillemanns, P, Runnebaum, IB, Antonenkova, N, Butzow, R, Leminen, A, Nevanlinna, H, Pelttari, LM, Edwards, RP, Kelley, JL, Modugno, F, Moysich, KB, Ness, RB, Cannioto, R, Høgdall, E, Jensen, A, Giles, GG, Bruinsma, F, Kjaer, SK, Hildebrandt, MAT, Liang, D, Lu, KH, Wu, X, Bisogna, M, Dao, F, Levine, DA, Cramer, DW & Australian Ovarian Cancer Study 2015, 'Shared genetics underlying epidemiological association between endometriosis and ovarian cancer', Human Molecular Genetics, bind 24, nr. 20, s. 5955-64. https://doi.org/10.1093/hmg/ddv306

@article{958f3370eabd47779d3c3cc656cf24ae,

title = "Shared genetics underlying epidemiological association between endometriosis and ovarian cancer",

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.",

author = "Yi Lu and Gabriel Cuellar-Partida and Painter, {Jodie N} and Nyholt, {Dale R} and Morris, {Andrew P} and Fasching, {Peter A} and Alexander Hein and Stefanie Burghaus and Beckmann, {Matthias W} and Diether Lambrechts and {Van Nieuwenhuysen}, Els and Ignace Vergote and Adriaan Vanderstichele and Doherty, {Jennifer Anne} and Rossing, {Mary Anne} and Wicklund, {Kristine G} and Jenny Chang-Claude and Ursula Eilber and Anja Rudolph and Shan Wang-Gohrke and Goodman, {Marc T} and Natalia Bogdanova and Thilo D{\"o}rk and Matthias D{\"u}rst and Peter Hillemanns and Runnebaum, {Ingo B} and Natalia Antonenkova and Ralf Butzow and Arto Leminen and Heli Nevanlinna and Pelttari, {Liisa M} and Edwards, {Robert P} and Kelley, {Joseph L} and Francesmary Modugno and Moysich, {Kirsten B} and Ness, {Roberta B} and Rikki Cannioto and Estrid H{\o}gdall and Allan Jensen and Giles, {Graham G} and Fiona Bruinsma and Kjaer, {Susanne K} and Hildebrandt, {Michelle A T} and Dong Liang and Lu, {Karen H} and Xifeng Wu and Maria Bisogna and Fanny Dao and Levine, {Douglas A} and Cramer, {Daniel W} and {Australian Ovarian Cancer Study}",

year = "2015",

month = jun,

day = "5",

doi = "10.1093/hmg/ddv306",

language = "English",

volume = "24",

pages = "5955--64",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

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T1 - Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

AU - Lu, Yi

AU - Cuellar-Partida, Gabriel

AU - Painter, Jodie N

AU - Nyholt, Dale R

AU - Morris, Andrew P

AU - Fasching, Peter A

AU - Hein, Alexander

AU - Burghaus, Stefanie

AU - Beckmann, Matthias W

AU - Lambrechts, Diether

AU - Van Nieuwenhuysen, Els

AU - Vergote, Ignace

AU - Vanderstichele, Adriaan

AU - Doherty, Jennifer Anne

AU - Rossing, Mary Anne

AU - Wicklund, Kristine G

AU - Chang-Claude, Jenny

AU - Eilber, Ursula

AU - Rudolph, Anja

AU - Wang-Gohrke, Shan

AU - Goodman, Marc T

AU - Bogdanova, Natalia

AU - Dörk, Thilo

AU - Dürst, Matthias

AU - Hillemanns, Peter

AU - Runnebaum, Ingo B

AU - Antonenkova, Natalia

AU - Butzow, Ralf

AU - Leminen, Arto

AU - Nevanlinna, Heli

AU - Pelttari, Liisa M

AU - Edwards, Robert P

AU - Kelley, Joseph L

AU - Modugno, Francesmary

AU - Moysich, Kirsten B

AU - Ness, Roberta B

AU - Cannioto, Rikki

AU - Høgdall, Estrid

AU - Jensen, Allan

AU - Giles, Graham G

AU - Bruinsma, Fiona

AU - Kjaer, Susanne K

AU - Hildebrandt, Michelle A T

AU - Liang, Dong

AU - Lu, Karen H

AU - Wu, Xifeng

AU - Bisogna, Maria

AU - Dao, Fanny

AU - Levine, Douglas A

AU - Cramer, Daniel W

AU - Australian Ovarian Cancer Study

PY - 2015/6/5

Y1 - 2015/6/5

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddv306

DO - 10.1093/hmg/ddv306

M3 - Journal article

C2 - 26231222

SN - 0964-6906

VL - 24

SP - 5955

EP - 5964

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 20

ER -

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

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