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

Br J Cancer. 2018 Apr;118(8):1123-1129. doi: 10.1038/s41416-018-0011-3. Epub 2018 Mar 20.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Height / genetics
  • Body Height / physiology*
  • Carcinoma, Ovarian Epithelial / epidemiology*
  • Carcinoma, Ovarian Epithelial / genetics
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Geography
  • Humans
  • Mendelian Randomization Analysis
  • Middle Aged
  • Ovarian Neoplasms / epidemiology*
  • Ovarian Neoplasms / genetics
  • Risk Factors
  • Young Adult

Grant support