Taller stature linked to elevated ovarian cancer risk
Women with a genetic propensity to being taller appear to be at greater risk of developing ovarian cancer, suggesting the involvement of genes influencing height in pathways promoting ovarian carcinogenesis, according to a study.
“Using Mendelian randomization, we have established that the previously observed association between height and ovarian cancer risk is unlikely to have been explained by bias,” the authors said. “Height could therefore be used, with other risk factors, to identify women at elevated risk.”
In the study, the authors pooled data from 39 Ovarian Cancer Association Consortium studies including 16,395 ovarian cancer cases and 23,003 controls. The median age of the participants at diagnosis or interview was 56 years. Mean height ranged between 159 and 167 cm across 22 studies with data, 163 cm for controls vs 164 cm for cases (p<0.0001).
Results from a Mendelian randomization meta-analysis, performed using a weighted genetic risk score (GRS) combining 609 single-nucleotide polymorphisms (SNPs), showed an association between genetically predicted height and ovarian cancer risk.
Specifically, there was a modest increase in the risk of developing ovarian cancer in women with greater genetically predicted height (per 5 cm increase in height: pooled odds ratio [OR], 1.06; 95 percent CI, 1.01–1.11). This relationship was more pronounced for borderline tumours (pooled OR, 1.15; 1.02–1.29) than for invasive tumours (pooled OR, 1.06; 1.01–1.11). [Br J Cancer 2018;118:1123-1129]
“The GRS-menarche age association is unlikely to explain the observed association, because age at menarche is only weakly associated with ovarian cancer, and women with later menarche have if anything lower ovarian cancer risk, so if this affected our results, we would expect the true effect to be at least as strong as the reported association,” they explained, adding that removing hormone-related SNPs, or adjusting for menarche age, did not attenuate estimates.
“Despite potential limitations of conventional observational studies, our Mendelian randomization-estimate is almost identical to previously reported associations, suggesting previous estimates were not appreciably biased,” the authors continued. [PLoS Med 2012;9:e1001200; Cancer Epidemiol Biomark Prev 2008;17:902-912; Cancer Epidemiol Biomark Prev 2005;14:2045-2048]
Additional studies are warranted to explore mechanisms underpinning the association between genetically predicted height and ovarian cancer risk, they said.