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

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Dixon-Suen, SC; Nagle, CM; Thrift, AP; Pharoah, PDP; Ewing, A; Pearce, CL; Zheng, W; Chenevix-Trench, G; Fasching, PA; Beckmann, MW; ...Date
2018-04-01Source Title
British Journal of CancerPublisher
NATURE PUBLISHING GROUPUniversity of Melbourne Author/s
Southey, Melissa; Campbell, Ian; Giles, Graham; Bruinsma, Fiona; Milne, RogerAffiliation
Sir Peter MacCallum Department of OncologyMelbourne School of Population and Global Health
Clinical Pathology
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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), pp.1123-1129. https://doi.org/10.1038/s41416-018-0011-3.Access Status
Open AccessAbstract
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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