Dataset Information

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 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]

PMID: 29555990

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Project description:To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status.Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors.UK Biobank.119,669 men and women of British ancestry, aged between 37 and 73 years.Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index.In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6 × 10(-3)) lower annual household income in men and a £1890 (£1680 to £2100; P=6 × 10(-15)) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6 × 10(-7)), and a £1130 (£680 to £1580) higher annual household income (P=4 × 10(-8)). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m(2)) caused a £2940 (£1680 to £4200; P=1 × 10(-5)) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only.These data support evidence that height and BMI play an important partial role in determining several aspects of a person's socioeconomic status, especially women's BMI for income and deprivation and men's height for education, income, and job class. These findings have important social and health implications, supporting evidence that overweight people, especially women, are at a disadvantage and that taller people, especially men, are at an advantage.

Project description:BackgroundObservational studies have investigated the association of risk factors with breast cancer prognosis. However, the results have been conflicting and it has been challenging to establish causality due to potential residual confounding. Using a Mendelian randomisation (MR) approach, we aimed to examine the potential causal association between breast cancer-specific survival and nine established risk factors for breast cancer: alcohol consumption, body mass index, height, physical activity, mammographic density, age at menarche or menopause, smoking, and type 2 diabetes mellitus (T2DM).MethodsWe conducted a two-sample MR analysis on data from the Breast Cancer Association Consortium (BCAC) and risk factor summary estimates from the GWAS Catalog. The BCAC data included 86,627 female patients of European ancestry with 7054 breast cancer-specific deaths during 15 years of follow-up. Of these, 59,378 were estrogen receptor (ER)-positive and 13,692 were ER-negative breast cancer patients. For the significant association, we used sensitivity analyses and a multivariable MR model. All risk factor associations were also examined in a model adjusted by other prognostic factors.ResultsIncreased genetic liability to T2DM was significantly associated with worse breast cancer-specific survival (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.03-1.17, P value [P] = 0.003). There were no significant associations after multiple testing correction for any of the risk factors in the ER-status subtypes. For the reported significant association with T2DM, the sensitivity analyses did not show evidence for violation of the MR assumptions nor that the association was due to increased BMI. The association remained significant when adjusting by other prognostic factors.ConclusionsThis extensive MR analysis suggests that T2DM may be causally associated with worse breast cancer-specific survival and therefore that treating T2DM may improve prognosis.

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

Publications

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

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