학술논문
Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study
Document Type
article
Author
Dixon-Suen, Suzanne C; Nagle, Christina M; Thrift, Aaron P; Pharoah, Paul DP; Ewing, Ailith; Pearce, Celeste Leigh; Zheng, Wei; Australian Ovarian Cancer Study Group; Chenevix-Trench, Georgia; Fasching, Peter A; Beckmann, Matthias W; Lambrechts, Diether; Vergote, Ignace; Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Chang-Claude, Jenny; Jung, Audrey Y; Moysich, Kirsten B; Odunsi, Kunle; Goodman, Marc T; Wilkens, Lynne R; Thompson, Pamela J; Shvetsov, Yurii B; Dörk, Thilo; Park-Simon, Tjoung-Won; Hillemanns, Peter; Bogdanova, Natalia; Butzow, Ralf; Nevanlinna, Heli; Pelttari, Liisa M; Leminen, Arto; Modugno, Francesmary; Ness, Roberta B; Edwards, Robert P; Kelley, Joseph L; Heitz, Florian; du Bois, Andreas; Harter, Philipp; Schwaab, Ira; Karlan, Beth Y; Lester, Jenny; Orsulic, Sandra; Rimel, Bobbie J; Kjær, Susanne K; Høgdall, Estrid; Jensen, Allan; Goode, Ellen L; Fridley, Brooke L; Cunningham, Julie M; Winham, Stacey J; Giles, Graham G; Bruinsma, Fiona; Milne, Roger L; Southey, Melissa C; Hildebrandt, Michelle AT; Wu, Xifeng; Lu, Karen H; Liang, Dong; Levine, Douglas A; Bisogna, Maria; Schildkraut, Joellen M; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Bandera, Elisa V; Olson, Sara H; Salvesen, Helga B; Thomsen, Liv Cecilie Vestrheim; Kopperud, Reidun K; Bjorge, Line; Kiemeney, Lambertus A; Massuger, Leon FAG; Pejovic, Tanja; Bruegl, Amanda; Cook, Linda S; Le, Nhu D; Swenerton, Kenneth D; Brooks-Wilson, Angela; Kelemen, Linda E; Lubiński, Jan; Huzarski, Tomasz; Gronwald, Jacek; Menkiszak, Janusz; Wentzensen, Nicolas; Brinton, Louise; Yang, Hannah; Lissowska, Jolanta; Høgdall, Claus K; Lundvall, Lene; Song, Honglin; Tyrer, Jonathan P; Campbell, Ian; Eccles, Diana; Paul, James; Glasspool, Rosalind; Siddiqui, Nadeem; Whittemore, Alice S
Source
British Journal of Cancer. 118(8)
Subject
Language
Abstract
BackgroundObservational 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.MethodsWe 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.ResultsGreater 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.ConclusionsWomen 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.