Abstract
BACKGROUND: Previous preclinical studies have revealed the biological links between cardiovascular diseases (CVD) and cancer. However, population-based evidence remained inconclusive. METHODS: We assessed cancer incidence among individuals with and without CVD condition in a prospective cohort from the UK Biobank (UKB). Multivariable Cox regression and competing risk models were fitted to estimate hazard ratios (HR). A systematic literature search was conducted in Medline, Embase and Cochrane Library databases to identify published population-based cohort studies (last updated on 1 October 2023) investigating the associations between CVD status and subsequent cancer risk. Random-effects meta-analysis was employed to pool relative effect estimates reported by eligible cohorts. Subgroup and sensitivity analyses were conducted to evaluate the associations across various CVD and cancer subtypes. RESULTS: For the cohort study in the UKB, after a median follow-up of 11.58 years, a total of 18,471 and 66,891 cancer cases occurred among 94,845 CVD patients and 368,695 non-CVD individuals (Incidence rate: 25.62 vs. 15.41 per 1000 person-years). Individuals with prior CVD exhibited higher overall cancer risk (HR 1.14, 95% CI 1.12-1.17, p < 0.001), and we observed consistently higher cancer risk after adjusting for competing risk from non-cancer deaths. The effect size of CVD on cancer risk was greater among younger individuals (< 65 years) than those ≥ 65 years (p for interaction < 0.001). The meta-analysis included 47 population-based cohort studies where a total of 1.49 million cancer cases were documented among over 45 million participants (9.49 million CVD patients). A 13% higher risk of overall cancer was observed among individuals with prior CVD (pooled RR 1.13, 95% CI 1.11-1.15, p < 0.001). The associations remained significant between various CVD subtypes and cancer risk at multiple sites. CONCLUSIONS: Our study identified a significantly higher cancer risk among individuals with CVD conditions compared with the non-CVD population, underpinning the need for continued cancer surveillance among CVD patients and further exploration of the possible etiological relation between CVD and cancer.