Genetic meta-analysis of cancer diagnosis following statin use identifies new associations and implicates human leukocyte antigen (HLA) in women.
Maxine SunAudrey LemaçonMarc-André LegaultGéraldine AsselinSylvie ProvostHugues AschardAmina BarhdadiYassamin Feroz ZadaDiane ValoisIan MongrainJean Claude TardifMarie-Pierre DubéPublished in: The pharmacogenomics journal (2021)
We sought to perform a genomic evaluation of the risk of incident cancer in statin users, free of cancer at study entry. Patients who previously participated in two phase IV trials (TNT and IDEAL) with genetic data were used (npooled = 11,196). A GWAS meta-analysis using Cox modeling for the prediction of incident cancer was conducted in the pooled cohort and sex-stratified. rs13210472 (near HLA-DOA gene) was associated with higher risk of incident cancer amongst women with prevalent coronary artery disease (CAD) taking statins (hazard ratio [HR]: 2.66, 95% confidence interval [CI]: 1.88-3.76, P = 3.5 × 10-8). Using the UK Biobank and focusing exclusively on women statin users with CAD (nfemale = 2952), rs13210472 remained significantly associated with incident cancer (HR: 1.71, 95% CI: 1.14-2.56, P = 9.0 × 10-3). The association was not observed in non-statin users. In this genetic meta-analysis, we have identified a variant in women statin users with prevalent CAD that was associated with incident cancer, possibly implicating the human leukocyte antigen pathway.
Keyphrases
- coronary artery disease
- papillary thyroid
- cardiovascular disease
- systematic review
- squamous cell
- endothelial cells
- genome wide
- childhood cancer
- gene expression
- percutaneous coronary intervention
- clinical trial
- copy number
- polycystic ovary syndrome
- squamous cell carcinoma
- randomized controlled trial
- cross sectional
- heart failure
- young adults
- cardiovascular events
- transcription factor
- electronic health record
- coronary artery bypass grafting
- study protocol
- low density lipoprotein