BACKGROUND AND PURPOSE:

• There is emerging evidence that Lynch Syndrome (LS) is associated with additional cancer types beyond colorectal and endometrial cancer
• Negro et al. (eClinicalMedicine, 2025) evaluated the incidence of non-colorectal/endometrial cancers in individuals with LS

METHODS:

• Retrospective cohort study
  • Data derived from 2 centers in Italy
  • Between 1995 and 2023
• Population
  • Patients with LS
• Exposures
  • Mismatch repair proteins (MMRs) immunohistochemistry detected gene mutations
• Study design
  • Standardized incidence ratios (SIRs) were calculated, with adjustment for
    • Age | Sex | Country
• Primary outcome
  • Cancer type
  • Age at diagnosis
  • Time to LS confirmation

RESULTS:

• 570 patients with LS
  • Median age at diagnosis of LS: 50 (IQR, 38 to 61) years
• Malignancies detected
  • Colorectal cancer: 44% of patients
  • Endometrial cancer: 17% of patients
  • Non-colorectal or endometrial cancer: 40%
• Most common types of non-colorectal/endometrial cancer
  • Urothelial: 8%
  • Breast: 8%
  • Ovarian: 6%
  • Gastric: 4%
• Cancers with the highest standardized incidence ratios
  • Small intestine: SIR 10.54 (95% CI, 5.90 to 17.39)
  • Urothelium/kidney: SIR 7.55 (95% CI, 5.42 to 10.24)
  • Gastric: SIR 4.68 (95% CI, 2.90 to 7.16)
  • Ovary: SIR 3.80 (95% CI, 2.32 to 5.87)
  • Pancreas: SIR 3.09 (95% CI, 1.69 to 5.18)
• Patients diagnosed with non-colorectal/endometrial cancers before genetic testing: 11%
  • Later developed colorectal or endometrial cancer: 46%
  • Median time to onset
    • Colorectal cancer: 10 (IQR, 5 to 15) years
    • Endometrial cancer: 6 (IQR, 2 to 9) years

CONCLUSION:

• 40% of LS patients were diagnosed with a non-colorectal or endometrial cancer
• 11% of these diagnoses occurred before genetic testing
• The authors state

The spectrum of extracolonic malignancies linked to the syndrome is broader than previously recognized and differs significantly from the original descriptions

In addition to the well-established malignancies, a growing number of additional cancers are emerging as candidates for inclusion in LS spectrum

Learn More – Primary Sources:

Incidence of non-colorectal/endometrial malignancies in individuals with Lynch syndrome: a retrospective cohort study