Cancer risk in myotonic dystrophy type 1: an updated systematic review and meta-analysis

Background Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disorder caused by expansion of a CTG trinucleotide repeat in the 3′ untranslated region of the DMPK gene. Several studies have reported increased cancer incidence in individuals with DM1, but estimates have varied and a previous meta-analysis was limited by studies with small sample sizes. We performed an updated systematic review and meta-analysis to quantify overall and site-specific cancer risk in DM1. Methods MEDLINE, Embase and Web of Science were searched from database inception to 6 January 2026. Studies reporting cancer incidence in individuals with DM1 were included. Standardised incidence ratios (SIRs) were pooled using random-effects meta-analysis. Hazard ratios and relative risks reported by studies using alternative comparator populations were summarised descriptively. Heterogeneity was assessed using I², Cochran's Q, tau-squared and 95% prediction intervals. Results Eleven studies met inclusion criteria. Five studies comprising 7,443 individuals with DM1 contributed data to the primary meta-analysis. The pooled Standardised Incidence Ratio (SIR) for all cancers was 1.74 (95% CI 1.51-2.00; I²=40.6%). Site-specific analyses demonstrated significant increases in risk for ovarian cancer (SIR 8.08, 95% CI 3.92–16.67), uterine cancer (SIR 7.15, 95% CI 4.72–10.83), brain cancer (SIR 6.68, 95% CI 4.06–11.01), thyroid cancer (SIR 5.45, 95% CI 2.14–13.91), pancreatic cancer (SIR 3.69, 95% CI 2.02–6.75), liver cancer (SIR 2.97, 95% CI 1.89–4.68), lymphoma (SIR 2.20, 95% CI 1.17–4.15), melanoma (SIR 1.92, 95% CI 1.10–3.36) and colorectal cancer (SIR 1.92, 95% CI 1.41–2.60). Breast and lung cancer were not significantly elevated. Heterogeneity was low for most site-specific analyses. Conclusions Individuals with DM1 experience a significantly increased incidence of cancer. Cancer risk is not uniformly elevated across tissues, with marked increases observed for selected malignancies and little evidence of excess risk for others. These findings support enhanced awareness of cancer susceptibility in DM1 and suggest that DM1 may provide a useful model for investigating relationships between somatic repeat instability and carcinogenesis.