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

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.

SUBMITTER: Dixon-Suen SC 

PROVIDER: S-EPMC5931085 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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

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

British journal of cancer 20180320 8

<h4>Background</h4>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.<h4>Methods</h4>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 p  ...[more]