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

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; Doerk, T; Park-Simon, T-W; 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; Kjaer, SK; Hogdall, 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; Lubinski, J; Huzarski, T; Gronwald, J; Menkiszak, J; Wentzensen, N; Brinton, L; Yang, H; Lissowska, J; Hogdall, 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, C-C; Kupryjanczyk, J; Dansonka-Mieszkowska, A; Budzilowska, A; Rzepecka, IK; Webb, PM

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Author

Dixon-Suen, SC; Nagle, CM; Thrift, AP; Pharoah, PDP; Ewing, A; Pearce, CL; Zheng, W; Chenevix-Trench, G; Fasching, PA; Beckmann, MW; ...

Date

2018-04-01

Source Title

British Journal of Cancer

Publisher

NATURE PUBLISHING GROUP

University of Melbourne Author/s

Southey, Melissa; Campbell, Ian; Giles, Graham; Bruinsma, Fiona; Milne, Roger

Affiliation

Sir Peter MacCallum Department of Oncology
Melbourne School of Population and Global Health
Clinical Pathology

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Document Type

Journal Article

Citations

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), pp.1123-1129. https://doi.org/10.1038/s41416-018-0011-3.

Access Status

Open Access

URI

http://hdl.handle.net/11343/256255

DOI

10.1038/s41416-018-0011-3

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.

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