The APC p.I1307K polymorphism is a significant risk factor for CRC in average risk Ashkenazi Jews

Eur J Cancer. 2013 Nov;49(17):3680-5. doi: 10.1016/j.ejca.2013.06.040. Epub 2013 Jul 26.

Abstract

Background: The p.I1307K adenomatous polyposis coli (APC) gene variant, prevalent among Ashkenazi Jews, may increase the risk for colorectal neoplasia. We studied the clinical importance of screening for this polymorphism in 3305 Israelis undergoing colonoscopy.

Patients and methods: Clinical data regarding potential risk factors for colorectal cancer (CRC) were collected from individuals undergoing colonoscopic examination at the Tel-Aviv medical center. The APC p.I1307K was detected using real-time PCR (polymerase chain reaction) from DNA extracted from peripheral mononuclear cells.

Results: The overall prevalence of the p.I1307K polymorphism was 8.0% (10.1% among Ashkenazi and 2.7% among Sephardic Jews, p<0.001). The overall adjusted odds ratio (OR) for colorectal neoplasia among carriers was 1.51 (95% confidence intervals (CI), 1.16-1.98). Among average risk Ashkenazi Jews, the adjusted OR was 1.75 (95% CI 1.26-2.45). A multiplicative interaction was identified between Ashkenazi ethnicity and APC p.I1307K carrier status (P(INTERACTION) = 0.055). The histopathological features of adenomas and carcinomas did not differ between carriers and non-carriers.

Conclusions: The APC p.I1307K gene variant is an important risk factor for colorectal neoplasia in average risk Ashkenazi Jews. Carriers in this group should be considered for screening colonoscopy at the age of 40, to be repeated every 5 years, similar to recommendations in individuals with family history of colorectal cancer.

Keywords: APC; Colorectal cancer; Polymorphism; Prevention; p.I1307K.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / ethnology
  • Colorectal Neoplasms / genetics*
  • Female
  • Genes, APC*
  • Genetic Predisposition to Disease / ethnology
  • Heterozygote
  • Humans
  • Israel / epidemiology
  • Jews / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors