Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study.
By: 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,
Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia. Suzanne.Dixon@qimrberghofer.edu.au.
2017-08-08; doi: 10.1038/s41416-018-0011-3
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.
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.
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.
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.
PMID:
29555990
