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.
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.
Rozen
Paul
P
Department of Gastroenterology, Tel Aviv Medical Center, 6 Weizmann Street, 64239  Tel Aviv, Israel. rozen@tasmc.health.gov.il
Naiman
Tova
T
Strul
Hana
H
Taussky
Philipp
P
Karminsky
Nataly
N
Shomrat
Ruth
R
Samuel
Ziona
Z
Yaron
Yuval
Y
Orr-Urtreger
Avi
A
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