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

Authors:
Suzanne C Dixon-Suen Christina M Nagle Aaron P Thrift Paul D P Pharoah Ailith Ewing Celeste Leigh Pearce Wei Zheng Georgia Chenevix-Trench Peter A Fasching Matthias W Beckmann Diether Lambrechts Ignace Vergote Sandrina Lambrechts Els Van Nieuwenhuysen Mary Anne Rossing Jennifer A Doherty Kristine G Wicklund Jenny Chang-Claude Audrey Y Jung Kirsten B Moysich Kunle Odunsi Marc T Goodman Lynne R Wilkens Pamela J Thompson Yurii B Shvetsov Thilo Dörk Tjoung-Won Park-Simon Peter Hillemanns Natalia Bogdanova Ralf Butzow Heli Nevanlinna Liisa M Pelttari Arto Leminen Francesmary Modugno Roberta B Ness Robert P Edwards Joseph L Kelley Florian Heitz Andreas du Bois Philipp Harter Ira Schwaab Beth Y Karlan Jenny Lester Sandra Orsulic Bobbie J Rimel Susanne K Kjær Estrid Høgdall Allan Jensen Ellen L Goode Brooke L Fridley Julie M Cunningham Stacey J Winham Graham G Giles Fiona Bruinsma Roger L Milne Melissa C Southey Michelle A T Hildebrandt Xifeng Wu Karen H Lu Dong Liang Douglas A Levine Maria Bisogna Joellen M Schildkraut Andrew Berchuck Daniel W Cramer Kathryn L Terry Elisa V Bandera Sara H Olson Helga B Salvesen Liv Cecilie Vestrheim Thomsen Reidun K Kopperud Line Bjorge Lambertus A Kiemeney Leon F A G Massuger Tanja Pejovic Amanda Bruegl Linda S Cook Nhu D Le Kenneth D Swenerton Angela Brooks-Wilson Linda E Kelemen Jan Lubiński Tomasz Huzarski Jacek Gronwald Janusz Menkiszak Nicolas Wentzensen Louise Brinton Hannah Yang Jolanta Lissowska Claus K Høgdall Lene Lundvall Honglin Song Jonathan P Tyrer Ian Campbell Diana Eccles James Paul Rosalind Glasspool Nadeem Siddiqui Alice S Whittemore Weiva Sieh Valerie McGuire Joseph H Rothstein Steven A Narod Catherine Phelan Harvey A Risch John R McLaughlin Hoda Anton-Culver Argyrios Ziogas Usha Menon Simon A Gayther Susan J Ramus Aleksandra Gentry-Maharaj Anna H Wu Malcolm C Pike Chiu-Chen Tseng Jolanta Kupryjanczyk Agnieszka Dansonka-Mieszkowska Agnieszka Budzilowska Iwona K Rzepecka Penelope M Webb

Br J Cancer 2018 04 20;118(8):1123-1129. Epub 2018 Mar 20.

Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia.

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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http://dx.doi.org/10.1038/s41416-018-0011-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931085PMC
April 2018
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