Towards gene- and gender-based risk estimates in Lynch syndrome; age-specific incidences for 13 extra-colorectal cancer types

BACKGROUND: In Lynch syndrome, inherited mismatch repair (MMR) defects predispose to colorectal cancer and to a wide spectrum of extra-colorectal tumours. Utilising a cohort study design, we aimed to determine the risk of extra-colorectal cancer and to identify yet unrecognised tumour types. METHODS: Data from 1624 Lynch syndrome mutation carriers in the Danish hereditary non-polyposis colorectal cancer register were used to estimate the sex- and age-specific incidence rate ratios (IRRs) for 30 extra-colorectal malignancies with comparison to the general population. RESULTS: Significantly increased IRRs were identified for 13 cancer types with differences related to gender, age and disease-predisposing gene. The different cancer types showed variable peak age incidence rates (IRs) with the highest IRs for ovarian cancer at age 30–49 years, for endometrial cancer, breast cancer, renal cell cancer and brain tumours at age 50–69 years, and for urothelial cancer, small bowel cancer, gastric cancer, pancreatic cancer and skin tumours after age 70. CONCLUSIONS: The broad spectrum of tumour types that develop at an increased incidence defines Lynch syndrome as a multi-tumour syndrome. The variable incidences in relation to age, gender and gene suggest a need for individualised surveillance.