Sex differences in cancer incidence and mortality in patients with cardiovascular disease: the European Prospective Investigation into Cancer-Norfolk study

BACKGROUND AND AIMS: The incidence of cancer in people with cardiovascular disease (CVD) is poorly understood. This study aimed to understand the sex differences in incident cancer and cancer-related mortality in people with and without CVD. METHODS: Participants were drawn from the European Prospective Investigation into Cancer (EPIC)-Norfolk study and followed up for a median of 26.2 years. Participants were stratified by sex and incident CVD during follow-up. Cumulative cancer incidence was calculated for each group. Sex-specific lifetime risks of cancer were determined, accounting for competing risks of death. Cause-specific hazard ratios (HRs) were determined using Royston-Parmar models, adjusted for ethnicity and time-updated covariates, including deprivation index, cardiovascular risk factors, comorbidities, and medication. Participants' CVD status was updated throughout follow-up. RESULTS: A total of 22 534 participants were cancer-free at baseline (57% women; mean age 58.6 ± 9.3 and 59.5 ± 9.3 for women and men, respectively); 10 889 participants either had prevalent CVD at baseline or developed CVD during follow-up. Men had more comorbidities. The adjusted lifetime risk of incident cancer in CVD participants at age 75 was higher in men (17.3%) than in women (12.8%), with a significant cause-specific HR of 1.39 (99% confidence interval [CI] 1.25-1.53, P < .0001). Corresponding data for participants with no CVD were 10.2% for men and 8.2% for women, with an HR of 1.27 (99% CI 1.15-1.41, P < .0001 for men vs women). A similar trend exists for cancer-related mortality (HR 1.51, 99% CI 1.31-1.75, P < .0001 for men with CVD and HR 1.31, 99% CI 1.14-1.50, P < .0001 for men without CVD). CONCLUSIONS: This study showed an increased lifetime cancer risk and mortality in men compared with women, which was mediated by comorbid CVD.