Assessing the role of cortisol in cancer: a wide-ranged Mendelian randomisation study
Menée à l'aide d'une méthode de randomisation mendélienne et de données de la "UK Biobank" ou de la "FinnGen" ainsi qu'à partir de données génétiques concernant 3 variants liés au cortisol et issues d'une méta-analyse d'association sur le génome entier de 12 597 participants, cette étude analyse l'association entre le niveau de cortisol plasmatique et le risque de cancer
Background: Cortisol’s immunosuppressive, obesogenic, and hyperglycaemic effects suggest that it may play a role in cancer development. However, whether cortisol increases cancer risk is not known. We investigated the potential causal association between plasma cortisol and risk of overall and common site-specific cancers using Mendelian randomisation. Methods: Three genetic variants associated with morning plasma cortisol levels at the genome-wide significance level (P < 5 × 10−8) in the Cortisol Network consortium were used as genetic instruments. Summary-level genome-wide association study data for the cancer outcomes were obtained from large-scale cancer consortia, the UK Biobank, and the FinnGen consortium. Two-sample Mendelian randomisation analyses were performed using the fixed-effects inverse-variance weighted method. Estimates across data sources were combined using meta-analysis. Results: A standard deviation increase in genetically predicted plasma cortisol was associated with increased risk of endometrial cancer (odds ratio 1.50, 95% confidence interval 1.13–1.99; P = 0.005). There was no significant association between genetically predicted plasma cortisol and risk of other common site-specific cancers, including breast, ovarian, prostate, colorectal, lung, or malignant skin cancer, or overall cancer. Conclusions: These results indicate that elevated plasma cortisol levels may increase the risk of endometrial cancer but not other cancers. The mechanism by which this occurs remains to be investigated.