title: Clinical and screening implications of the I1307K adenomatous polyposis coli gene variant in Israeli Ashkenazi Jews with familial colorectal neoplasia. Evidence for a founder effect.
abstract: BACKGROUND
  The authors previously found the I1307K adenomatous polyposis coli (APC) gene variant in 5% of Ashkenazi control participants, in 15.4% of those who had familial colorectal neoplasia, but also in 1.6% of non-Ashkenazi control participants. In this study, they evaluated its use in a screening program for familial colorectal neoplasia and examined for a founder effect.
  
  
  METHODS
  Consecutive Ashkenazim with a personal and/or family history of colorectal neoplasia had the DNA test. Markers flanking the APC gene were examined in Ashkenazi and non-Ashkenazi I1307K carriers and noncarriers.
  
  
  RESULTS
  Among 718 persons, I1307K occurred in 6.2% of Ashkenazi participants, in 1.5% of non-Ashkenazi control participants (P = 0.02), and in 10.7% of Ashkenazim with familial neoplasia (relative risk, 1.73 [not significant compared with controls]; 95% confidence interval, 0.7-3.2). Colorectal neoplasia was detected in carriers at a younger age (P < 0.05) without excess risk for multiple colorectal neoplasia or noncolorectal neoplasia. I1307K attributable risk for colorectal neoplasia was 0.5-0.6%. Compared with noncarriers, both Ashkenazi and non-Ashkenazi I1307K carriers had similar flanking polymorphic alleles (P < 0.01).
  
  
  CONCLUSIONS
  I1307K is a low-penetrance genetic variant that indicates a 1.7 relative risk for neoplasia in carriers who have familial carcinoma, clinically equivalent to obtaining a family history of sporadic colorectal neoplasia and promoting early screening. I1307K is a founder genetic variant in Jews of different ethnic origin, mainly Ashkenazim, but it explains only partially their higher incidence of colorectal carcinoma.
authors.affiliation: Department of Gastroenterology, Tel Aviv Medical Center, 6 Weizmann Street, 64239  Tel Aviv, Israel. rozen@tasmc.health.gov.il
authors.forename: Paul
authors.initials: P
authors.lastname: Rozen
authors.forename: Tova
authors.initials: T
authors.lastname: Naiman
authors.forename: Hana
authors.initials: H
authors.lastname: Strul
authors.forename: Philipp
authors.initials: P
authors.lastname: Taussky
authors.forename: Nataly
authors.initials: N
authors.lastname: Karminsky
authors.forename: Ruth
authors.initials: R
authors.lastname: Shomrat
authors.forename: Ziona
authors.initials: Z
authors.lastname: Samuel
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yaron
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D017491:Genes, APC; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged