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Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study

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OBJECTIVE: To assess clinicopathological predictors and prognosis in early-onset colorectal cancer (CRC) in Lynch syndrome with comparison to patients diagnosed from age 40 and up.

DESIGN: National, retrospective register-based case-control study.

SETTING: Danish national hereditary CRC register.

PARTICIPANTS: Individuals with Lynch syndrome diagnosed with CRC from January 1950 to June 2020. The analysis was based on 215 early-onset CRCs diagnosed between 15 and 39 years of age and 574 CRCs diagnosed at age 40-88 years.

MAIN OUTCOME MEASURES: Clinical and histopathological characteristics and survival. Confounding variables were analysed by Cox analysis.

RESULTS: 27.2% of the tumours in the Danish Lynch syndrome cohort were diagnosed under age 40. Disease-predisposing alterations in MLH1 and MSH2 were overrepresented in the age 15-39 cohort compared with patients diagnosed over age 40. CRCs diagnosed under age 40 showed an adverse stage distribution with 36.2% stage III-IV tumours compared with 25.8% in the over age 40 group. However, young patients diagnosed with early-stage tumours did have a significantly better prognosis compared with early-stage tumours in the older age group.

CONCLUSIONS: Early-onset CRC in Lynch syndrome is primarily linked to alterations in MLH1 and MSH2 and displays an adverse stage distribution. These observations serve as a reminder of surveillance, symptom awareness and rapid diagnostic handling of CRC in young adults with Lynch syndrome.

Original languageEnglish
Article numbere053538
JournalBMJ Open
Issue number12
Pages (from-to)1-8
Number of pages8
Publication statusPublished - 15 Dec 2021

Bibliographical note

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

    Research areas

  • Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis, Colorectal Neoplasms/diagnosis, DNA Mismatch Repair, Denmark/epidemiology, Humans, Middle Aged, MutL Protein Homolog 1/genetics, Retrospective Studies, Young Adult, molecular aspects, cancer genetics, gastrointestinal tumours

ID: 70540587