Distinct Molecular Profiles of Sporadic Early-Onset Colorectal Cancer: A Population-Based Cohort and Systematic Review
Background and Aims: The observed increase in the incidence of early-onset colorectal cancer (EOCRC) is being driven by sporadic cases, but the molecular characteristics of these tumors are not fully understood. Our objective was to investigate the prevalence of microsatellite instability (MSI) and...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Gastro Hep Advances |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772572322001923 |
| _version_ | 1797843858148556800 |
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| author | Ashleigh C. Hamilton Finian J. Bannon Philip D. Dunne Jacqueline James Stephen McQuaid Ronan T. Gray Manuel Salto-Tellez Chris R. Cardwell Maurice B. Loughrey Helen G. Coleman |
| author_facet | Ashleigh C. Hamilton Finian J. Bannon Philip D. Dunne Jacqueline James Stephen McQuaid Ronan T. Gray Manuel Salto-Tellez Chris R. Cardwell Maurice B. Loughrey Helen G. Coleman |
| author_sort | Ashleigh C. Hamilton |
| collection | DOAJ |
| description | Background and Aims: The observed increase in the incidence of early-onset colorectal cancer (EOCRC) is being driven by sporadic cases, but the molecular characteristics of these tumors are not fully understood. Our objective was to investigate the prevalence of microsatellite instability (MSI) and selected mutations in sporadic EOCRC, and their association with survival. Methods: Firstly, we compared the prevalence of molecular characteristics and survival within a population-based cohort study of 652 stage II and III colon cancer patients in Northern Ireland, comparing sporadic early-onset (<50 years, n = 35) with older (60–69 years, n = 179) patients. Secondly, a systematic review for studies reporting the prevalence of MSI, mismatch repair deficiency (dMMR), or BRAF, KRAS, NRAS, PIK3CA, and TP53 mutations in sporadic EOCRC was conducted. A meta-analysis was performed to calculate pooled estimates of the prevalence of molecular features in sporadic EOCRC. Results: Firstly, within the cohort study, EOCRC patients did not have a significantly increased risk of colorectal cancer–specific death (adjusted hazard ratio 1.20; 95% confidence interval [CI] 0.61–2.39) compared with 60- to 69-year-olds. Second, 32 studies were included in the systematic review. The pooled analysis estimated a prevalence of 10% (95% CI 7%–14%) for MSI high/dMMR in sporadic EOCRC. BRAF and KRAS mutations had a prevalence of 1% (95% CI 0%–3%) and 32% (95% CI 23%–40%), respectively. Conclusion: The molecular characteristics of sporadic EOCRC differ from those of cancers in older adults, particularly regarding reduced prevalence of BRAF mutations. Ten percent of sporadic EOCRC display MSI high/dMMR. Further studies are needed to address survival in sporadic EOCRC cases and whether molecular profiles influence EOCRC outcomes in this patient group. |
| first_indexed | 2024-04-09T17:12:49Z |
| format | Article |
| id | doaj.art-8d691786c5d14cfba3e309cbd980f469 |
| institution | Directory Open Access Journal |
| issn | 2772-5723 |
| language | English |
| last_indexed | 2024-04-09T17:12:49Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gastro Hep Advances |
| spelling | doaj.art-8d691786c5d14cfba3e309cbd980f4692023-04-20T04:37:56ZengElsevierGastro Hep Advances2772-57232023-01-0123347359Distinct Molecular Profiles of Sporadic Early-Onset Colorectal Cancer: A Population-Based Cohort and Systematic ReviewAshleigh C. Hamilton0Finian J. Bannon1Philip D. Dunne2Jacqueline James3Stephen McQuaid4Ronan T. Gray5Manuel Salto-Tellez6Chris R. Cardwell7Maurice B. Loughrey8Helen G. Coleman9Centre for Public Health, Queen’s University Belfast, Northern Ireland, UK; Correspondence: Address correspondence to: Ashleigh C. Hamilton, MB BCh, BAO, MRCP, Centre for Public Health, Queen’s University Belfast, ICS-B Building, Royal Victoria Hospital Site, Grosvenor Rd, Belfast, Northern Ireland BT12 6BA, UK.Centre for Public Health, Queen’s University Belfast, Northern Ireland, UKPatrick G. Johnston Centre for Cancer Research, Queen’s University Belfast, Northern Ireland, UK; CRUK Beatson Institute, Glasgow, UKPatrick G. Johnston Centre for Cancer Research, Queen’s University Belfast, Northern Ireland, UK; Northern Ireland Biobank, Belfast, Northern Ireland, UK; Precision Medicine Centre of Excellence, Queen’s University Belfast, Northern Ireland, UKPatrick G. Johnston Centre for Cancer Research, Queen’s University Belfast, Northern Ireland, UK; Northern Ireland Biobank, Belfast, Northern Ireland, UKCentre for Public Health, Queen’s University Belfast, Northern Ireland, UK; South Eastern Health and Social Care Trust, Northern Ireland, UKPatrick G. Johnston Centre for Cancer Research, Queen’s University Belfast, Northern Ireland, UK; Precision Medicine Centre of Excellence, Queen’s University Belfast, Northern Ireland, UKCentre for Public Health, Queen’s University Belfast, Northern Ireland, UKCentre for Public Health, Queen’s University Belfast, Northern Ireland, UK; Patrick G. Johnston Centre for Cancer Research, Queen’s University Belfast, Northern Ireland, UK; Department of Cellular Pathology, Belfast Health and Social Care Trust, Northern Ireland, UKCentre for Public Health, Queen’s University Belfast, Northern Ireland, UK; Patrick G. Johnston Centre for Cancer Research, Queen’s University Belfast, Northern Ireland, UKBackground and Aims: The observed increase in the incidence of early-onset colorectal cancer (EOCRC) is being driven by sporadic cases, but the molecular characteristics of these tumors are not fully understood. Our objective was to investigate the prevalence of microsatellite instability (MSI) and selected mutations in sporadic EOCRC, and their association with survival. Methods: Firstly, we compared the prevalence of molecular characteristics and survival within a population-based cohort study of 652 stage II and III colon cancer patients in Northern Ireland, comparing sporadic early-onset (<50 years, n = 35) with older (60–69 years, n = 179) patients. Secondly, a systematic review for studies reporting the prevalence of MSI, mismatch repair deficiency (dMMR), or BRAF, KRAS, NRAS, PIK3CA, and TP53 mutations in sporadic EOCRC was conducted. A meta-analysis was performed to calculate pooled estimates of the prevalence of molecular features in sporadic EOCRC. Results: Firstly, within the cohort study, EOCRC patients did not have a significantly increased risk of colorectal cancer–specific death (adjusted hazard ratio 1.20; 95% confidence interval [CI] 0.61–2.39) compared with 60- to 69-year-olds. Second, 32 studies were included in the systematic review. The pooled analysis estimated a prevalence of 10% (95% CI 7%–14%) for MSI high/dMMR in sporadic EOCRC. BRAF and KRAS mutations had a prevalence of 1% (95% CI 0%–3%) and 32% (95% CI 23%–40%), respectively. Conclusion: The molecular characteristics of sporadic EOCRC differ from those of cancers in older adults, particularly regarding reduced prevalence of BRAF mutations. Ten percent of sporadic EOCRC display MSI high/dMMR. Further studies are needed to address survival in sporadic EOCRC cases and whether molecular profiles influence EOCRC outcomes in this patient group.http://www.sciencedirect.com/science/article/pii/S2772572322001923Microsatellite InstabilityMismatch RepairMutations |
| spellingShingle | Ashleigh C. Hamilton Finian J. Bannon Philip D. Dunne Jacqueline James Stephen McQuaid Ronan T. Gray Manuel Salto-Tellez Chris R. Cardwell Maurice B. Loughrey Helen G. Coleman Distinct Molecular Profiles of Sporadic Early-Onset Colorectal Cancer: A Population-Based Cohort and Systematic Review Gastro Hep Advances Microsatellite Instability Mismatch Repair Mutations |
| title | Distinct Molecular Profiles of Sporadic Early-Onset Colorectal Cancer: A Population-Based Cohort and Systematic Review |
| title_full | Distinct Molecular Profiles of Sporadic Early-Onset Colorectal Cancer: A Population-Based Cohort and Systematic Review |
| title_fullStr | Distinct Molecular Profiles of Sporadic Early-Onset Colorectal Cancer: A Population-Based Cohort and Systematic Review |
| title_full_unstemmed | Distinct Molecular Profiles of Sporadic Early-Onset Colorectal Cancer: A Population-Based Cohort and Systematic Review |
| title_short | Distinct Molecular Profiles of Sporadic Early-Onset Colorectal Cancer: A Population-Based Cohort and Systematic Review |
| title_sort | distinct molecular profiles of sporadic early onset colorectal cancer a population based cohort and systematic review |
| topic | Microsatellite Instability Mismatch Repair Mutations |
| url | http://www.sciencedirect.com/science/article/pii/S2772572322001923 |
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