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


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.

Type Journal
ISBN 1532-1827 (Electronic) 0007-0920 (Linking)
Authors Dixon-Suen, S. C.; Nagle, C. M.; Thrift, A. P.; Pharoah, P. D. P.; Ewing, A.; Pearce, C. L.; Zheng, W.; Australian Ovarian Cancer Study, Group; 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.; Moysich, K. B.; Odunsi, K.; Goodman, M. T.; Wilkens, L. R.; Thompson, P. J.; Shvetsov, Y. B.; Dork, T.; Park-Simon, T. W.; Hillemanns, P.; Bogdanova, N.; Butzow, R.; Nevanlinna, H.; Pelttari, L. M.; Leminen, A.; Modugno, F.; Ness, R. B.; Edwards, R. P.; Kelley, J. L.; Heitz, F.; du Bois, A.; Harter, P.; Schwaab, I.; Karlan, B. Y.; Lester, J.; Orsulic, S.; Rimel, B. J.; Kjaer, S. K.; Hogdall, E.; Jensen, A.; Goode, E. L.; Fridley, B. L.; Cunningham, J. M.; Winham, S. J.; Giles, G. G.; Bruinsma, F.; Milne, R. L.; Southey, M. C.; Hildebrandt, M. A. T.; Wu, X.; Lu, K. H.; Liang, D.; Levine, D. A.; Bisogna, M.; Schildkraut, J. M.; Berchuck, A.; Cramer, D. W.; Terry, K. L.; Bandera, E. V.; Olson, S. H.; Salvesen, H. B.; Thomsen, L. C. V.; Kopperud, R. K.; Bjorge, L.; Kiemeney, L. A.; Massuger, Lfag; Pejovic, T.; Bruegl, A.; Cook, L. S.; Le, N. D.; Swenerton, K. D.; Brooks-Wilson, A.; Kelemen, L. E.; Lubinski, J.; Huzarski, T.; Gronwald, J.; Menkiszak, J.; Wentzensen, N.; Brinton, L.; Yang, H.; Lissowska, J.; Hogdall, C. K.; Lundvall, L.; Song, H.; Tyrer, J. P.; Campbell, I.; Eccles, D.; Paul, J.; Glasspool, R.; Siddiqui, N.; Whittemore, A. S., et al.
Publisher Name British Journal of Cancer
Published Date 2018-04-01
Published Volume 118
Published Issue 8
Published Pages 1123-1129
Status Published in-print
DOI 10.1038/s41416-018-0011-3
URL link to publisher's version
OpenAccess link to author's accepted manuscript version