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 C...

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Detalles Bibliográficos
Autores principales: Dixon-Suen, Suzanne C., Nagle, Christina M., Thrift, Aaron P., Pharoah, Paul D. P., Ewing, Ailith, Pearce, Celeste Leigh, Zheng, Wei, 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 A. T., 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 F. A. G., 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., Sieh, Weiva, McGuire, Valerie, Rothstein, Joseph H., Narod, Steven A., Phelan, Catherine, Risch, Harvey A., McLaughlin, John R., Anton-Culver, Hoda, Ziogas, Argyrios, Menon, Usha, Gayther, Simon A., Ramus, Susan J., Gentry-Maharaj, Aleksandra, Wu, Anna H., Pike, Malcolm C., Tseng, Chiu-Chen, Kupryjanczyk, Jolanta, Dansonka-Mieszkowska, Agnieszka, Budzilowska, Agnieszka, Rzepecka, Iwona K., Webb, Penelope M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931085/
https://www.ncbi.nlm.nih.gov/pubmed/29555990
http://dx.doi.org/10.1038/s41416-018-0011-3
Descripción
Sumario: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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