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

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.Particip...

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Main Authors: Thomas Kallemose, Mef Nilbert, Jon Ambæk Durhuus, Christina Therkildsen
Format: Article
Language:English
Published: BMJ Publishing Group 2021-12-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/11/12/e053538.full
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author Thomas Kallemose
Mef Nilbert
Jon Ambæk Durhuus
Christina Therkildsen
author_facet Thomas Kallemose
Mef Nilbert
Jon Ambæk Durhuus
Christina Therkildsen
author_sort Thomas Kallemose
collection DOAJ
description 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.
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spelling doaj-art-c002890bb25c477ea2218eefb0b5d9e22025-08-20T01:59:13ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2021-053538Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based studyThomas Kallemose0Mef Nilbert1Jon Ambæk Durhuus2Christina Therkildsen32 Department of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, DenmarkDepartment of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, DenmarkDepartment of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, DenmarkDepartment of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, DenmarkObjective 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.https://bmjopen.bmj.com/content/11/12/e053538.full
spellingShingle Thomas Kallemose
Mef Nilbert
Jon Ambæk Durhuus
Christina Therkildsen
Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study
BMJ Open
title Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study
title_full Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study
title_fullStr Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study
title_full_unstemmed Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study
title_short Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study
title_sort colorectal cancer in adolescents and young adults with lynch syndrome a danish register based study
url https://bmjopen.bmj.com/content/11/12/e053538.full
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