Somatic mosaic chromosomal alterations and death of cardiovascular disease causes among cancer survivors: an analysis of the UK Biobank

Cancer survivors are at an increased risk of cardiovascular disease (CVD) compared to the general population. Here, we evaluated the impact of somatic mosaic chromosomal alterations (mCAs) on death of CVD causes, coronary artery disease (CAD) causes, from cancer, and of any cause in patients with a cancer diagnosis within the UK Biobank (n=48 919). mCAs were derived from DNA genotyping array intensity data and long-range chromosomal phase inference from participants. Overall, 10 070 individuals (20.6%) carried ≥1 mCA clone. In adjusted analyses, mCA was associated with an increased risk of death of CAD causes (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.09-1.71, P =0.006), from cancer (HR: 1.06, 95% CI: 1.00-1.11, P =0.041), and death of any cause (HR: 1.07, 95% CI: 1.02-1.12, P =0.005). Among cancer survivors, carriers of any mCA are at an increased risk of death of CAD causes and of any cause as compared to non-carriers. ### Competing Interest Statement M-P.D. has received personal fees and reports minor equity interest in Dalcor Pharmaceuticals. M-P.D. has a patent Methods for Treating or Preventing Cardiovascular Disorders and Lowering Risk of Cardiovascular Events issued to Dalcor Pharmaceuticals, no royalties received; a patent Genetic Markers for Predicting Responsiveness to Therapy with HDL-Raising or HDL Mimicking Agent issued to Dalcor Pharmaceuticals, no royalties received; and a patent Methods for using low dose colchicine after myocardial infarction, assigned to the Montreal Heart Institute. J-C.T. reports research grants from Amarin, AstraZeneca, Ceapro, DalCor Pharmaceuticals, Esperion, Ionis, Novartis, Pfizer, and RegenXBio; honoraria from AstraZeneca, DalCor Pharmaceuticals, HLS Pharmaceuticals, Pendopharm and Pfizer; minor equity interest from Dalcor Pharmaceuticals; and authorship on a patent Methods for Treating or Preventing Cardiovascular Disorders and Lowering Risk of Cardiovascular Events issued to Dalcor Pharmaceuticals, no royalties received; a patent Genetic Markers for Predicting Responsiveness to Therapy with HDL-Raising or HDL Mimicking Agent issued to Dalcor Pharmaceuticals, no royalties received; a pending patent Early administration of low-dose colchicine after myocardial infarction, and a patent Methods for using low-dose colchicine after myocardial infarction, assigned to the Montreal Heart Institute (J-C.T. has waived his rights in the colchicine patents). Other authors have nothing to declare. ### Funding Statement M.S. was funded by a doctorate scholarship from the Fonds de Recherche du Quebec - Sante (FRQS). M-P.D. and J-C.T. hold Canada Research Chairs. This project was funded in part by the Health Collaboration Acceleration Fund (FACS) from the Government of Quebec (J-C.T. principal investigator and M-P.D. co-principal investigator). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used only openly available human data that were originally located at https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors