Introduction: About 20% of colorectal cancer (CRC) patients show some kind of familiarity, which might be caused by yet unknown combinations of low penetrance susceptibility genes. We aimed to identify genetic factors for familial CRC (fCRC) in a unique study design that includes phenotypic extremes as represented by fCRC cases and 'hyper-normal' controls without CRC history and no adenomatous polyps on colonoscopy.
Materials And Methods: Candidate gene variants were determined by allele-specific amplification (SLC10A2 c.169C>T and c.171G>T) and restriction fragment length polymorphism assays (CCND1 c.870A>G; CDH1 -160C>A; TP53 R72P; VDR T2M). In total, 98 patients with fCRC, 96 patients with sporadic CRC, and 220 hyper-normal controls were included.
Results: The minor allele of the CDH1 -160C>A polymorphism occurred significantly more often in controls compared to fCRC cases (OR = 0.664; p = 0.042). Homozygosity of the minor allele was significantly associated with affiliation to the control group (OR = 0.577; p = 0.029), indicating that both heterozygous and homozygous carriers of the common allele are at-risk for CRC. With respect to the CCND1 c.870A>G mutation, comparison of fCRC and sporadic CRC cases showed that A/A homozygosity was more common than G/G homozygosity among fCRC patients compared to controls (OR = 2.119; p = 0.045). However, no differences in allele or genotype frequencies were detected between sporadic CRC cases and controls, and no associations were observed for SLC10A2, TP53, and VDR polymorphisms.
Conclusions: We report a potential association of variants in the CCND1 and CDH1 genes with fCRC using a unique study design with phenotypic extremes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00384-007-0388-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Deficient Mismatch Repair and BRAF Mutations in Metastatic Colorectal Cancer in the South Island of New Zealand.
Asia Pac J Clin Oncol
January 2025
Wellington Blood and Cancer Centre, Health New Zealand/Te Whatu Ora - Capital, Coast and Hutt Valley, Wellington, New Zealand.
Aim: Manatū Hauora, the Ministry of Health of New Zealand (NZ), published minimum standards for molecular testing of colorectal cancers (CRCs) in June 2018. These included mismatch repair (MMR) testing at diagnosis and BRAFV600E mutation analysis on newly diagnosed stage IV CRCs. This study aimed to determine the proportion of patients with CRC in the South Island of NZ with metastatic deficient mismatch repair (dMMR) CRC, the proportion of metastatic CRCs and dMMR CRCs that have a BRAFV600E mutation, and audit testing for BRAF mutations and appropriate referral to genetics services.
View Article and Find Full Text PDFAdenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications.
Transl Oncol
January 2025
Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3010, Australia; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3010, Australia. Electronic address: https://twitter.com/petergeorgeson.
Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.
Methods: Whole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelic MUTYH cases, on 7 adenomas and 2 CRCs from 5 biallelic NTHL1 cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants.
Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors.
Front Immunol
January 2025
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Background: Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.
Methods: Including 1,236 CRC tumors from three observational studies, we conducted T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay.
Prognosis of early-onset versus late-onset sporadic colorectal cancer: Systematic review and meta-analysis.
Eur J Cancer
January 2025
Digestive Surgery, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti, 435, Milan 20141, Italy. Electronic address:
Article Synopsis
- There has been a concerning rise in early-onset colorectal cancer (EO-CRC) cases, prompting research into how prognosis compares to late-onset colorectal cancer (LO-CRC).
- A systematic review of 26 studies found that EO-CRC patients are more likely to be diagnosed at advanced stages, yet they have better overall survival rates compared to LO-CRC patients, while other survival metrics like cancer-specific survival remain similar.
- The study highlights the need for better early detection methods for EO-CRC due to the differences in stage at diagnosis between the two groups.
Candidate Genetic Loci Modifying the Colorectal Cancer Risk Caused by Lifestyle Risk Factors.
Clin Transl Gastroenterol
November 2024
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Introduction: 65%-70% of colorectal cancer (CRC) cases are considered sporadic; they arise under the influence of environmental factors in individuals lacking a family history of CRC. Low-risk genetic variants are believed to contribute to CRC risk, in tandem with lifestyle factors.
Methods: Six hundred sixteen nonfamilial Swedish CRC cases with at least 1 of the following 5 risk factors: smoking, excessive alcohol consumption, physical inactivity, adherence to an unhealthy diet, and excess body weight were included in this study.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!