{
  "abstract": "Background APC c.3920T>A; p.Ile1307Lys (I1307K), prevalent in individuals of Ashkenazi Jewish (AJ) origin, has been associated with a modestly increased colorectal cancer (CRC) risk. Clinical recommendations for I1307K heterozygotes vary across countries and expert groups, reflecting differences in population frequencies, modest risk estimates and limited data in non-AJ individuals.Methods We analysed UK Biobank data comprising 466 315 individuals (8944 with CRC), using genomic analysis to classify AJ and non-AJ ancestries.Results I1307K was identified in 7.1% of AJ and 0.08% of non-AJ white participants. No significant association with CRC was observed in AJ (OR: 0.71; 95% CI: 0.17 to 2.95) or non-AJ white individuals (OR: 1.05; 95% CI: 0.50 to 2.22). The previously established OR of 1.7–1.8 for AJ individuals lies within our 95% CI, indicating underpowered results due to limited CRC cases. No significant associations were detected for other cancers. Unbiased, adequately powered CRC case–control studies in non-AJ populations would require cohorts far larger than current resources for feasible analysis.Conclusion Clinical actionability of I1307K should prioritise risk stratification based on overall CRC risk and ancestry-dependent variant detection rates. However, management strategies need not differ by ancestry once a carrier is identified, as the biological impact of I1307K should be consistent across populations.",
  "authors": [
    {
      "affiliations": [
        "Division of Genetics and Epidemiology, The Institute of Cancer Research, London, England, UK"
      ],
      "name": "Sophie Allen"
    },
    {
      "affiliations": [
        "Division of Genetics and Epidemiology, The Institute of Cancer Research, London, England, UK"
      ],
      "name": "Charlie F Rowlands"
    },
    {
      "affiliations": [
        "The Polyposis Registry, St Mark’s Centre for Familial Intestinal Cancer, Saint Mark’s Hospital, London, England, UK",
        "Department of Surgery and Cancer, Imperial College London, London, England, UK"
      ],
      "name": "Andrew Latchford"
    },
    {
      "affiliations": [
        "Division of Genetics and Epidemiology, The Institute of Cancer Research, London, England, UK",
        "Royal Marsden Hospital NHS Trust, London, England, UK"
      ],
      "name": "Clare Turnbull"
    },
    {
      "affiliations": [
        "Hereditary Cancer Programme, Catalan Institute of Oncology",
        "Oncobell Programme, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain",
        "CIBERONC, Madrid, Spain"
      ],
      "name": "Laura Valle"
    }
  ],
  "title": "APC I1307K and clinical management: insights from UK Biobank association analysis of colorectal and other cancer risks in Ashkenazi and non-Ashkenazi whites",
  "uid": "aae95d2f-f3ad-5024-88e1-5d7c506dee69"
}