Publications by authors named "I Frayling"
Colorectal cancer (CRC) is a common cancer in Ireland. Of all CRCs, 2-4% are attributable to Lynch Syndrome (LS), the most common CRC predisposition syndrome. LS is caused by constitutional pathogenic variants (PVs) affecting mismatch repair (MMR) genes with resultant MMR protein deficiency (dMMR).
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- - Pathogenic variants in the APC gene are responsible for familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome, prompting the development of specific classification criteria to aid in variant interpretation.
- - The study involved applying these APC-specific criteria to assess over 10,000 unique APC variants from databases like ClinVar and LOVD, leading to a significant reclassification of variants of uncertain significance (VUSs), with many being reassessed as (likely) benign or (likely) pathogenic.
- - The results showed that using these tailored criteria effectively reduced VUSs by 37%, highlighted the potential for systematic variant classification in large datasets, and established a model that could benefit future genetic variant interpretation efforts in
Article Synopsis
- Globally, while people are living longer, many experience a decline in health due to age-related diseases, highlighting the need for better classification systems to address these issues.
- A consensus meeting with 150 experts established criteria for identifying ageing-related pathologies, requiring a 70% agreement for approval among participants.
- The agreed criteria focus on conditions that progress with age, contribute to functional decline, and are backed by human studies, setting a foundation for future classification and staging efforts.
Article Synopsis
- - Lynch syndrome (LS) is a genetic condition that increases the risk of certain cancers due to defects in DNA mismatch repair genes, and cancer risk estimates based on family history may be biased.
- - A study involving 830 MMR gene variant carriers from the UK Biobank found significantly higher cumulative incidences of colorectal and endometrial cancers by age 70 compared to non-carriers, but no significant difference for breast cancer.
- - The findings suggest that individuals with pathogenic variants in MMR genes should receive surveillance for colorectal cancer and interventions for endometrial cancer risk, while breast cancer does not appear to be linked to LS.
Article Synopsis
- The study focused on improving the classification of genetic variants linked to familial adenomatous polyposis using APC-specific criteria developed by an expert panel.
- A total of 10,228 unique variants were analyzed, resulting in 41% of VUS from ClinVar and 61% from LOVD being reclassified, primarily as (Likely) Benign, which reduced the overall VUS by 37%.
- The research highlighted a systematic approach to variant classification in large datasets that could be applied to other gene/disease interpretations and allowed for prioritization of VUS requiring further evidence collection.