Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Abstract

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.

Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.

Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I² = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I² = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I² = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I² = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I² = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.

Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.

Fig. 1. Random-effects meta-analysis of the association between diabetes and total cancer risk.

Models were adjusted for country, age (years), smoking status (never/ever), educational level (primary or less/primary or less than college or university/college or university), alcohol consumption (g/day), BMI, (kg/m²) and vigorous physical activity (yes/no). The size of each box indicates the relative weight of each study in the meta-analysis; the horizontal bars show the 95% confidence intervals (CI). Diamonds represent the combined HRs and 95% CI.

Fig. 2. Random-effects meta-analysis of the association between diabetes and colorectal cancer risk.

Models were adjusted for country, age (years), smoking status (never/ever), educational level (primary or less/primary or less than college or university/college or university), alcohol consumption (g/day), BMI, (kg/m²) and vigorous physical activity (yes/no). The size of each box indicates the relative weight of each study in the meta-analysis; the horizontal bars show the 95% confidence intervals (CI). Diamonds represent the combined HRs and 95% CI.

Fig. 3. Random-effects meta-analysis of the association between diabetes and prostate cancer risk.

Models were adjusted for country, age (years), smoking status (never/ever), educational level (primary or less/primary or less than college or university/college or university), alcohol consumption (g/day), BMI, (kg/m²) and vigorous physical activity (yes/no). The size of each box indicates the relative weight of each study in the meta-analysis; the horizontal bars show the 95% confidence intervals (CI). Diamonds represent the combined HRs and 95% CI.