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

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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 languageEnglish (US)
Pages (from-to)1123-1129
Number of pages7
JournalBritish Journal of Cancer
Volume118
Issue number8
DOIs
StatePublished - Apr 1 2018

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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