title: APC I1307K increases risk of transition from polyp to colorectal carcinoma in Ashkenazi Jews.
abstract: OBJECTIVE
  The I1307K allele of the APC gene has been shown to confer a modestly elevated risk of colorectal cancer in the Ashkenazi Jewish population (relative risk, 1.5-1.7). However, it is unclear whether the alteration predisposes to adenomas and whether the genetic information can be used in clinical practice. To further address the pathogenic significance of I1307K, we offered both a genetic test and a screening program to individuals considered to be at increased risk for colorectal cancer. We compared the prevalence of polyps and their characteristics between carriers and noncarriers.
  
  
  METHODS
  Invitations to participate in a DNA and colonoscopy screening program were mailed, together with a family questionnaire, to 3540 households forming the Jewish Community in Ottawa. The I1307K variant was analyzed in 242 eligible respondents who were selected because they had a personal or family history of colon cancer. Nearly 80% of these respondents (n = 189; age range, 32-83 years) consented to undergo a single colonoscopic examination.
  
  
  RESULTS
  The overall carrier frequency of I1307K in the study group was 10.3%. A higher proportion of heterozygous gene carriers was found in the subgroup of colon cancer survivors (27%) than among asymptomatic individuals (8%, P < 0.02). A total of 59 polyps were identified in 44 subjects. Histologically confirmed adenomatous polyps were diagnosed in 11.8% of carriers and 12.8% of noncarriers (P > 0.5). No significant differences in polyp size, multiplicity, location, degree of villosity, or age-dependent prevalence were found between the 2 groups of participants.
  
  
  CONCLUSIONS
  The high frequency of I1307K colorectal cancer patients found in the Ashkenazi Jewish community of Ottawa and the equivalent proportion of carriers and noncarriers who developed adenomatous polyps suggest that in this community, I1307K is associated with a significant predisposition to carcinoma but not adenoma.
authors.affiliation: Loeb Health Research Institute, Ottawa Hospital Civic Campus, Ottawa, Ontario, Canada. hartley.stern@orcc.on.ca
authors.forename: H S
authors.initials: HS
authors.lastname: Stern
authors.forename: S
authors.initials: S
authors.lastname: Viertelhausen
authors.forename: A G
authors.initials: AG
authors.lastname: Hunter
authors.forename: K
authors.initials: K
authors.lastname: O'Rourke
authors.forename: M
authors.initials: M
authors.lastname: Cappelli
authors.forename: H
authors.initials: H
authors.lastname: Perras
authors.forename: K
authors.initials: K
authors.lastname: Serfas
authors.forename: A
authors.initials: A
authors.lastname: Blumenthall
authors.forename: D
authors.initials: D
authors.lastname: Dewar
authors.forename: E
authors.initials: E
authors.lastname: Baumann
authors.forename: A E
authors.initials: AE
authors.lastname: Lagarde
mesh_terms: D018256:Adenomatous Polyps / Q000208:ethnology* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015179:Colorectal Neoplasms / Q000208:ethnology* / Q000235:genetics*; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D017491:Genes, APC / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors