Adult height is associated with increased risk of ovarian cancer: A Mendelian randomisation study

Suzanne C. Dixon-Suen; Christina M. Nagle; Aaron P. Thrift; Paul D.P. Pharoah; Ailith Ewing; Celeste Leigh Pearce; Wei Zheng; Georgia Chenevix-Trench; Peter A. Fasching; Matthias W. Beckmann; Diether Lambrechts; Ignace Vergote; Sandrina Lambrechts; Els Van Nieuwenhuysen; Mary Anne Rossing; Jennifer A. Doherty; Kristine G. Wicklund; Jenny Chang-Claude; Audrey Y. Jung; Kirsten B. Moysich; Kunle Odunsi; Marc T. Goodman; Lynne R. Wilkens; Pamela J. Thompson; Yurii B. Shvetsov; Thilo Dörk; Tjoung Won Park-Simon; Peter Hillemanns; Natalia Bogdanova; Ralf Butzow; Heli Nevanlinna; Liisa M. Pelttari; Arto Leminen; Francesmary Modugno; Roberta B. Ness; Robert P. Edwards; Joseph L. Kelley; Florian Heitz; Andreas Du Bois; Philipp Harter; Ira Schwaab; Beth Y. Karlan; Jenny Lester; Sandra Orsulic; Bobbie J. Rimel; Susanne K. Kjær; Estrid Høgdall; Allan Jensen; Ellen L. Goode; Brooke L. Fridley; Julie M. Cunningham; Stacey J. Winham; Graham G. Giles; Fiona Bruinsma; Roger L. Milne; Melissa C. Southey; Michelle A.T. Hildebrandt; Xifeng Wu; Karen H. Lu; Dong Liang; Douglas A. Levine; Maria Bisogna; Joellen M. Schildkraut; Andrew Berchuck; Daniel W. Cramer; Kathryn L. Terry; Elisa V. Bandera; Sara H. Olson; Helga B. Salvesen; Liv Cecilie Vestrheim Thomsen; Reidun K. Kopperud; Line Bjorge; Lambertus A. Kiemeney; Leon F.A.G. Massuger; Tanja Pejovic; Amanda Bruegl; Linda S. Cook; Nhu D. Le; Kenneth D. Swenerton; Angela Brooks-Wilson; Linda E. Kelemen; Jan Lubiński; Tomasz Huzarski; Jacek Gronwald; Janusz Menkiszak; Nicolas Wentzensen; Louise Brinton; Hannah Yang; Jolanta Lissowska; Claus K. Høgdall; Lene Lundvall; Honglin Song; Jonathan P. Tyrer; Ian Campbell; Diana Eccles; James Paul; Rosalind Glasspool; Nadeem Siddiqui; Alice S. Whittemore; Weiva Sieh; Valerie McGuire; Joseph H. Rothstein; Steven A. Narod; Catherine Phelan; Harvey A. Risch; John R. McLaughlin; Hoda Anton-Culver; Argyrios Ziogas; Usha Menon; Simon A. Gayther; Susan J. Ramus; Aleksandra Gentry-Maharaj; Anna H. Wu; Malcolm C. Pike; Chiu Chen Tseng; Jolanta Kupryjanczyk; Agnieszka Dansonka-Mieszkowska; Agnieszka Budzilowska; Iwona K. Rzepecka; Penelope M. Webb

doi:10.1038/s41416-018-0011-3

Adult height is associated with increased risk of ovarian cancer: A Mendelian randomisation study

Suzanne C. Dixon-Suen, Christina M. Nagle, Aaron P. Thrift, Paul D.P. Pharoah, Ailith Ewing, Celeste Leigh Pearce, Wei Zheng, Georgia Chenevix-Trench, Peter A. Fasching, Matthias W. Beckmann, Diether Lambrechts, Ignace Vergote, Sandrina Lambrechts, Els Van Nieuwenhuysen, Mary Anne Rossing, Jennifer A. Doherty, Kristine G. Wicklund, Jenny Chang-Claude, Audrey Y. Jung, Kirsten B. MoysichKunle Odunsi, Marc T. Goodman, Lynne R. Wilkens, Pamela J. Thompson, Yurii B. Shvetsov, Thilo Dörk, Tjoung Won Park-Simon, Peter Hillemanns, Natalia Bogdanova, Ralf Butzow, Heli Nevanlinna, Liisa M. Pelttari, Arto Leminen, Francesmary Modugno, Roberta B. Ness, Robert P. Edwards, Joseph L. Kelley, Florian Heitz, Andreas Du Bois, Philipp Harter, Ira Schwaab, Beth Y. Karlan, Jenny Lester, Sandra Orsulic, Bobbie J. Rimel, Susanne K. Kjær, Estrid Høgdall, Allan Jensen, Ellen L. Goode, Brooke L. Fridley, Julie M. Cunningham, Stacey J. Winham, Graham G. Giles, Fiona Bruinsma, Roger L. Milne, Melissa C. Southey, Michelle A.T. Hildebrandt, Xifeng Wu, Karen H. Lu, Dong Liang, Douglas A. Levine, Maria Bisogna, Joellen M. Schildkraut, Andrew Berchuck, Daniel W. Cramer, Kathryn L. Terry, Elisa V. Bandera, Sara H. Olson, Helga B. Salvesen, Liv Cecilie Vestrheim Thomsen, Reidun K. Kopperud, Line Bjorge, Lambertus A. Kiemeney, Leon F.A.G. Massuger, Tanja Pejovic, Amanda Bruegl, Linda S. Cook, Nhu D. Le, Kenneth D. Swenerton, Angela Brooks-Wilson, Linda E. Kelemen, Jan Lubiński, Tomasz Huzarski, Jacek Gronwald, Janusz Menkiszak, Nicolas Wentzensen, Louise Brinton, Hannah Yang, Jolanta Lissowska, Claus K. Høgdall, Lene Lundvall, Honglin Song, Jonathan P. Tyrer, Ian Campbell, Diana Eccles, James Paul, Rosalind Glasspool, Nadeem Siddiqui, Alice S. Whittemore, Weiva Sieh, Valerie McGuire, Joseph H. Rothstein, Steven A. Narod, Catherine Phelan, Harvey A. Risch, John R. McLaughlin, Hoda Anton-Culver, Argyrios Ziogas, Usha Menon, Simon A. Gayther, Susan J. Ramus, Aleksandra Gentry-Maharaj, Anna H. Wu, Malcolm C. Pike, Chiu Chen Tseng, Jolanta Kupryjanczyk, Agnieszka Dansonka-Mieszkowska, Agnieszka Budzilowska, Iwona K. Rzepecka, Penelope M. Webb

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Background: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias. Methods: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis. Results: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours. Conclusions: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

Original language	English
Pages (from-to)	1123-1129
Number of pages	7
Journal	British Journal of Cancer
Volume	118
Issue number	8
DOIs	https://doi.org/10.1038/s41416-018-0011-3
State	Published - 1 Apr 2018

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10.1038/s41416-018-0011-3

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Dixon-Suen, S. C., Nagle, C. M., Thrift, A. P., Pharoah, P. D. P., Ewing, A., Pearce, C. L., Zheng, W., Chenevix-Trench, G., Fasching, P. A., Beckmann, M. W., Lambrechts, D., Vergote, I., Lambrechts, S., Van Nieuwenhuysen, E., Rossing, M. A., Doherty, J. A., Wicklund, K. G., Chang-Claude, J., Jung, A. Y., ... Webb, P. M. (2018). Adult height is associated with increased risk of ovarian cancer: A Mendelian randomisation study. British Journal of Cancer, 118(8), 1123-1129. https://doi.org/10.1038/s41416-018-0011-3

@article{907faf116f5a46cc953191f5bbb14d08,

title = "Adult height is associated with increased risk of ovarian cancer: A Mendelian randomisation study",

abstract = "Background: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias. Methods: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis. Results: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours. Conclusions: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.",

author = "Dixon-Suen, {Suzanne C.} and Nagle, {Christina M.} and Thrift, {Aaron P.} and Pharoah, {Paul D.P.} and Ailith Ewing and Pearce, {Celeste Leigh} and Wei Zheng and Georgia Chenevix-Trench and Fasching, {Peter A.} and Beckmann, {Matthias W.} and Diether Lambrechts and Ignace Vergote and Sandrina Lambrechts and {Van Nieuwenhuysen}, Els and Rossing, {Mary Anne} and Doherty, {Jennifer A.} and Wicklund, {Kristine G.} and Jenny Chang-Claude and Jung, {Audrey Y.} and Moysich, {Kirsten B.} and Kunle Odunsi and Goodman, {Marc T.} and Wilkens, {Lynne R.} and Thompson, {Pamela J.} and Shvetsov, {Yurii B.} and Thilo D{\"o}rk and Park-Simon, {Tjoung Won} and Peter Hillemanns and Natalia Bogdanova and Ralf Butzow and Heli Nevanlinna and Pelttari, {Liisa M.} and Arto Leminen and Francesmary Modugno and Ness, {Roberta B.} and Edwards, {Robert P.} and Kelley, {Joseph L.} and Florian Heitz and {Du Bois}, Andreas and Philipp Harter and Ira Schwaab and Karlan, {Beth Y.} and Jenny Lester and Sandra Orsulic and Rimel, {Bobbie J.} and Kj{\ae}r, {Susanne K.} and Estrid H{\o}gdall and Allan Jensen and Goode, {Ellen L.} and Fridley, {Brooke L.} and Cunningham, {Julie M.} and Winham, {Stacey J.} and Giles, {Graham G.} and Fiona Bruinsma and Milne, {Roger L.} and Southey, {Melissa C.} and Hildebrandt, {Michelle A.T.} and Xifeng Wu and Lu, {Karen H.} and Dong Liang and Levine, {Douglas A.} and Maria Bisogna and Schildkraut, {Joellen M.} and Andrew Berchuck and Cramer, {Daniel W.} and Terry, {Kathryn L.} and Bandera, {Elisa V.} and Olson, {Sara H.} and Salvesen, {Helga B.} and Thomsen, {Liv Cecilie Vestrheim} and Kopperud, {Reidun K.} and Line Bjorge and Kiemeney, {Lambertus A.} and Massuger, {Leon F.A.G.} and Tanja Pejovic and Amanda Bruegl and Cook, {Linda S.} and Le, {Nhu D.} and Swenerton, {Kenneth D.} and Angela Brooks-Wilson and Kelemen, {Linda E.} and Jan Lubi{\'n}ski and Tomasz Huzarski and Jacek Gronwald and Janusz Menkiszak and Nicolas Wentzensen and Louise Brinton and Hannah Yang and Jolanta Lissowska and H{\o}gdall, {Claus K.} and Lene Lundvall and Honglin Song and Tyrer, {Jonathan P.} and Ian Campbell and Diana Eccles and James Paul and Rosalind Glasspool and Nadeem Siddiqui and Whittemore, {Alice S.} and Weiva Sieh and Valerie McGuire and Rothstein, {Joseph H.} and Narod, {Steven A.} and Catherine Phelan and Risch, {Harvey A.} and McLaughlin, {John R.} and Hoda Anton-Culver and Argyrios Ziogas and Usha Menon and Gayther, {Simon A.} and Ramus, {Susan J.} and Aleksandra Gentry-Maharaj and Wu, {Anna H.} and Pike, {Malcolm C.} and Tseng, {Chiu Chen} and Jolanta Kupryjanczyk and Agnieszka Dansonka-Mieszkowska and Agnieszka Budzilowska and Rzepecka, {Iwona K.} and Webb, {Penelope M.}",

note = "Funding Information: Funding: This work was supported by: the National Cancer Institute at the U.S. National Institutes of Health [K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN025403, N01-CN55424, N01-PC67001, N01-PC67010, P01-CA17054, P30-CA072720, P30-CA008748, P30-CA14089, P30-CA15083, P50-CA105009, P50-CA136393, P50-CA159981, R01-CA058860, R01 CA063678, R01 CA063682, R01-CA092044, R01-CA095023, R01-CA16056, R01-CA54419, R01-CA58598, R01-CA61107, R01-CA61132, R01-CA76016, R01-CA83918, R01-CA87538, R01-CA112523, R01-CA122443, R03-CA113148, R03-CA115195, U01-CA69417, U01-CA71966 and Intramural Research funds]; the European Commission's Seventh Framework Programme [agreement number 223175 HEALTH F2 2009-223175]; Cancer Research UK [C490/A16561, C536/A13086, C536/A6689, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565]; a National Institutes of Health (CA128978), Cancer Post-GWAS Initiative [1U19 CA148537, 1U19 CA148065 and 1U19 CA148112—the Genetic Associations and Mechanisms in Oncology (GAME‐ON) initiative]; the U.S. Department of Defense [DAMD17-02-1-0669, W81XWH-07-0449, DAMD17-02-1-0666, W81XWH-10-1-0280 and W81XWH-10-1-0341]; the Canadian Institutes of Health Research (CIHR) [MOP-86727 and MSH-87734 to L.E.K.] and the CIHR Team in Familial Risks of Breast Cancer; the Komen Foundation for the Cure; the Breast Cancer Research Foundation; the Ovarian Cancer Research Fund (thanks to donations by the family and friends of Kathryn Sladek Smith); the U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729 and DAMD17-02-1-0669]; the National Health and Medical Research Council of Australia [199600, 209057, 251553, 400281, 504711, 1073898 and fellowships to G.C.-T. and P.M.W.]; Cancer Councils of Queensland, Victoria, New South Wales, South Australia and Tasmania and the Cancer Foundation of Western Australia [Multi-State Grant Applications 191, 211 and 182]; VicHealth; the ELAN Program of the University of Erlangen-Nuremberg; the Nationaal Kankerplan of Belgium; the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01 GB 9401]; the German Cancer Research Center; the Roswell Park Cancer Institute Alliance Foundation [P30 CA016056]; the Rudolf-Bartling Foundation; the Helsinki University Central Hospital Research Fund; the National Institutes of Health/National Center for Research Resources/General Clinical Research Center [M01-RR000056]; an American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN to B.Y.K.]; the National Center for Advancing Translational Sciences (NCATS) [UL1TR000124 to B.Y. K.]; the Danish Cancer Society [94-222-52]; the Mermaid I project; the Mayo Foundation; the Minnesota Ovarian Cancer Alliance; the Fred C. and Katherine B. Andersen Foundation; the Cancer Institute of New Jersey; Helse Vest; the Norwegian Cancer Society; the Research Council of Norway; Radboud University Medical Centre; the Oregon Health and Science University (OHSU) Foundation; Pomeranian Medical University; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, University College London Hospital, and the Royal Marsden Hospital; the Imperial Experimental Cancer Research Centre [C1312/ A15589]; the U.S. Public Health Service [PSA-042205]; the Lon V. Smith Foundation [LVS-39420]; The Eve Appeal; The Oak Foundation; the California Cancer Research Program [00-01389V-20170 and 2II0200]; the Polish Ministry of Science and Higher Education [4 PO5C 028 14 and 2 PO5A 068 27]; and the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw. Publisher Copyright: {\textcopyright} 2018 Cancer Research UK.",

year = "2018",

month = apr,

day = "1",

doi = "10.1038/s41416-018-0011-3",

language = "English",

volume = "118",

pages = "1123--1129",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "8",

}

Dixon-Suen, SC, Nagle, CM, Thrift, AP, Pharoah, PDP, Ewing, A, Pearce, CL, Zheng, W, Chenevix-Trench, G, Fasching, PA, Beckmann, MW, Lambrechts, D, Vergote, I, Lambrechts, S, Van Nieuwenhuysen, E, Rossing, MA, Doherty, JA, Wicklund, KG, Chang-Claude, J, Jung, AY, Moysich, KB, Odunsi, K, Goodman, MT, Wilkens, LR, Thompson, PJ, Shvetsov, YB, Dörk, T, Park-Simon, TW, Hillemanns, P, Bogdanova, N, Butzow, R, Nevanlinna, H, Pelttari, LM, Leminen, A, Modugno, F, Ness, RB, Edwards, RP, Kelley, JL, Heitz, F, Du Bois, A, Harter, P, Schwaab, I, Karlan, BY, Lester, J, Orsulic, S, Rimel, BJ, Kjær, SK, Høgdall, E, Jensen, A, Goode, EL, Fridley, BL, Cunningham, JM, Winham, SJ, Giles, GG, Bruinsma, F, Milne, RL, Southey, MC, Hildebrandt, MAT, Wu, X, Lu, KH, Liang, D, Levine, DA, Bisogna, M, Schildkraut, JM, Berchuck, A, Cramer, DW, Terry, KL, Bandera, EV, Olson, SH, Salvesen, HB, Thomsen, LCV, Kopperud, RK, Bjorge, L, Kiemeney, LA, Massuger, LFAG, Pejovic, T, Bruegl, A, Cook, LS, Le, ND, Swenerton, KD, Brooks-Wilson, A, Kelemen, LE, Lubiński, J, Huzarski, T, Gronwald, J, Menkiszak, J, Wentzensen, N, Brinton, L, Yang, H, Lissowska, J, Høgdall, CK, Lundvall, L, Song, H, Tyrer, JP, Campbell, I, Eccles, D, Paul, J, Glasspool, R, Siddiqui, N, Whittemore, AS, Sieh, W, McGuire, V, Rothstein, JH, Narod, SA, Phelan, C, Risch, HA, McLaughlin, JR, Anton-Culver, H, Ziogas, A, Menon, U, Gayther, SA, Ramus, SJ, Gentry-Maharaj, A, Wu, AH, Pike, MC, Tseng, CC, Kupryjanczyk, J, Dansonka-Mieszkowska, A, Budzilowska, A, Rzepecka, IK & Webb, PM 2018, 'Adult height is associated with increased risk of ovarian cancer: A Mendelian randomisation study', British Journal of Cancer, vol. 118, no. 8, pp. 1123-1129. https://doi.org/10.1038/s41416-018-0011-3

TY - JOUR

T1 - Adult height is associated with increased risk of ovarian cancer

T2 - A Mendelian randomisation study

AU - Dixon-Suen, Suzanne C.

AU - Nagle, Christina M.

AU - Thrift, Aaron P.

AU - Pharoah, Paul D.P.

AU - Ewing, Ailith

AU - Pearce, Celeste Leigh

AU - Zheng, Wei

AU - Chenevix-Trench, Georgia

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Lambrechts, Diether

AU - Vergote, Ignace

AU - Lambrechts, Sandrina

AU - Van Nieuwenhuysen, Els

AU - Rossing, Mary Anne

AU - Doherty, Jennifer A.

AU - Wicklund, Kristine G.

AU - Chang-Claude, Jenny

AU - Jung, Audrey Y.

AU - Moysich, Kirsten B.

AU - Odunsi, Kunle

AU - Goodman, Marc T.

AU - Wilkens, Lynne R.

AU - Thompson, Pamela J.

AU - Shvetsov, Yurii B.

AU - Dörk, Thilo

AU - Park-Simon, Tjoung Won

AU - Hillemanns, Peter

AU - Bogdanova, Natalia

AU - Butzow, Ralf

AU - Nevanlinna, Heli

AU - Pelttari, Liisa M.

AU - Leminen, Arto

AU - Modugno, Francesmary

AU - Ness, Roberta B.

AU - Edwards, Robert P.

AU - Kelley, Joseph L.

AU - Heitz, Florian

AU - Du Bois, Andreas

AU - Harter, Philipp

AU - Schwaab, Ira

AU - Karlan, Beth Y.

AU - Lester, Jenny

AU - Orsulic, Sandra

AU - Rimel, Bobbie J.

AU - Kjær, Susanne K.

AU - Høgdall, Estrid

AU - Jensen, Allan

AU - Goode, Ellen L.

AU - Fridley, Brooke L.

AU - Cunningham, Julie M.

AU - Winham, Stacey J.

AU - Giles, Graham G.

AU - Bruinsma, Fiona

AU - Milne, Roger L.

AU - Southey, Melissa C.

AU - Hildebrandt, Michelle A.T.

AU - Wu, Xifeng

AU - Lu, Karen H.

AU - Liang, Dong

AU - Levine, Douglas A.

AU - Bisogna, Maria

AU - Schildkraut, Joellen M.

AU - Berchuck, Andrew

AU - Cramer, Daniel W.

AU - Terry, Kathryn L.

AU - Bandera, Elisa V.

AU - Olson, Sara H.

AU - Salvesen, Helga B.

AU - Thomsen, Liv Cecilie Vestrheim

AU - Kopperud, Reidun K.

AU - Bjorge, Line

AU - Kiemeney, Lambertus A.

AU - Massuger, Leon F.A.G.

AU - Pejovic, Tanja

AU - Bruegl, Amanda

AU - Cook, Linda S.

AU - Le, Nhu D.

AU - Swenerton, Kenneth D.

AU - Brooks-Wilson, Angela

AU - Kelemen, Linda E.

AU - Lubiński, Jan

AU - Huzarski, Tomasz

AU - Gronwald, Jacek

AU - Menkiszak, Janusz

AU - Wentzensen, Nicolas

AU - Brinton, Louise

AU - Yang, Hannah

AU - Lissowska, Jolanta

AU - Høgdall, Claus K.

AU - Lundvall, Lene

AU - Song, Honglin

AU - Tyrer, Jonathan P.

AU - Campbell, Ian

AU - Eccles, Diana

AU - Paul, James

AU - Glasspool, Rosalind

AU - Siddiqui, Nadeem

AU - Whittemore, Alice S.

AU - Sieh, Weiva

AU - McGuire, Valerie

AU - Rothstein, Joseph H.

AU - Narod, Steven A.

AU - Phelan, Catherine

AU - Risch, Harvey A.

AU - McLaughlin, John R.

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Menon, Usha

AU - Gayther, Simon A.

AU - Ramus, Susan J.

AU - Gentry-Maharaj, Aleksandra

AU - Wu, Anna H.

AU - Pike, Malcolm C.

AU - Tseng, Chiu Chen

AU - Kupryjanczyk, Jolanta

AU - Dansonka-Mieszkowska, Agnieszka

AU - Budzilowska, Agnieszka

AU - Rzepecka, Iwona K.

AU - Webb, Penelope M.

N1 - Funding Information: Funding: This work was supported by: the National Cancer Institute at the U.S. National Institutes of Health [K07-CA095666, K07-CA80668, K07-CA143047, K22-CA138563, N01-CN025403, N01-CN55424, N01-PC67001, N01-PC67010, P01-CA17054, P30-CA072720, P30-CA008748, P30-CA14089, P30-CA15083, P50-CA105009, P50-CA136393, P50-CA159981, R01-CA058860, R01 CA063678, R01 CA063682, R01-CA092044, R01-CA095023, R01-CA16056, R01-CA54419, R01-CA58598, R01-CA61107, R01-CA61132, R01-CA76016, R01-CA83918, R01-CA87538, R01-CA112523, R01-CA122443, R03-CA113148, R03-CA115195, U01-CA69417, U01-CA71966 and Intramural Research funds]; the European Commission's Seventh Framework Programme [agreement number 223175 HEALTH F2 2009-223175]; Cancer Research UK [C490/A16561, C536/A13086, C536/A6689, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565]; a National Institutes of Health (CA128978), Cancer Post-GWAS Initiative [1U19 CA148537, 1U19 CA148065 and 1U19 CA148112—the Genetic Associations and Mechanisms in Oncology (GAME‐ON) initiative]; the U.S. Department of Defense [DAMD17-02-1-0669, W81XWH-07-0449, DAMD17-02-1-0666, W81XWH-10-1-0280 and W81XWH-10-1-0341]; the Canadian Institutes of Health Research (CIHR) [MOP-86727 and MSH-87734 to L.E.K.] and the CIHR Team in Familial Risks of Breast Cancer; the Komen Foundation for the Cure; the Breast Cancer Research Foundation; the Ovarian Cancer Research Fund (thanks to donations by the family and friends of Kathryn Sladek Smith); the U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729 and DAMD17-02-1-0669]; the National Health and Medical Research Council of Australia [199600, 209057, 251553, 400281, 504711, 1073898 and fellowships to G.C.-T. and P.M.W.]; Cancer Councils of Queensland, Victoria, New South Wales, South Australia and Tasmania and the Cancer Foundation of Western Australia [Multi-State Grant Applications 191, 211 and 182]; VicHealth; the ELAN Program of the University of Erlangen-Nuremberg; the Nationaal Kankerplan of Belgium; the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research [01 GB 9401]; the German Cancer Research Center; the Roswell Park Cancer Institute Alliance Foundation [P30 CA016056]; the Rudolf-Bartling Foundation; the Helsinki University Central Hospital Research Fund; the National Institutes of Health/National Center for Research Resources/General Clinical Research Center [M01-RR000056]; an American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN to B.Y.K.]; the National Center for Advancing Translational Sciences (NCATS) [UL1TR000124 to B.Y. K.]; the Danish Cancer Society [94-222-52]; the Mermaid I project; the Mayo Foundation; the Minnesota Ovarian Cancer Alliance; the Fred C. and Katherine B. Andersen Foundation; the Cancer Institute of New Jersey; Helse Vest; the Norwegian Cancer Society; the Research Council of Norway; Radboud University Medical Centre; the Oregon Health and Science University (OHSU) Foundation; Pomeranian Medical University; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, University College London Hospital, and the Royal Marsden Hospital; the Imperial Experimental Cancer Research Centre [C1312/ A15589]; the U.S. Public Health Service [PSA-042205]; the Lon V. Smith Foundation [LVS-39420]; The Eve Appeal; The Oak Foundation; the California Cancer Research Program [00-01389V-20170 and 2II0200]; the Polish Ministry of Science and Higher Education [4 PO5C 028 14 and 2 PO5A 068 27]; and the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw. Publisher Copyright: © 2018 Cancer Research UK.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias. Methods: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis. Results: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours. Conclusions: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

AB - Background: Observational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias. Methods: We pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis. Results: Greater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours. Conclusions: Women with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.

UR - http://www.scopus.com/inward/record.url?scp=85044249910&partnerID=8YFLogxK

U2 - 10.1038/s41416-018-0011-3

DO - 10.1038/s41416-018-0011-3

M3 - Article

C2 - 29555990

AN - SCOPUS:85044249910

SN - 0007-0920

VL - 118

SP - 1123

EP - 1129

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 8

ER -

Adult height is associated with increased risk of ovarian cancer: A Mendelian randomisation study

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