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
✍ Scribed by Paul Rozen; Tova Naiman; Hana Strul; Philipp Taussky; Nataly Karminsky; Ruth Shomrat; Ziona Samuel; Yuval Yaron; Avi Orr-Urtreger
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 92 KB
- Volume
- 94
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
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. Cancer 2002;94:2561–8. © 2002 American Cancer Society.
DOI 10.1002/cncr.10529