TY - JOUR

T1 - Colorectal cancer in adolescents and young adults with Lynch syndrome

T2 - A Danish register-based study

AU - Durhuus, Jon Ambæk

AU - Therkildsen, Christina

AU - Kallemose, Thomas

AU - Nilbert, Mef

N1 - Publisher Copyright: ©

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - cancer genetics

KW - gastrointestinal tumours

KW - molecular aspects

U2 - 10.1136/bmjopen-2021-053538

DO - 10.1136/bmjopen-2021-053538

M3 - Journal article

C2 - 34911717

AN - SCOPUS:85122524776

VL - 11

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 12

M1 - e053538

ER -