APC I1307K polymorphism as a predictive factor for colorectal neoplasia recurrence.

Abstract

1526 Background: The use of surveillance colonoscopy to detect disease recurrence after initial colorectal neoplasia resection has increased significantly in the past decade. Currently, predictive factors at index colonoscopy include only histo-pathologic characteristics such as adenoma number, size, type and dysplasia. The goal of the current study is to identify additional factors (i.e., genetic markers) that increase the risk of subsequent lesions and may optimize the use of surveillance colonoscopies. Methods: A prospective analysis of 383 consecutive Israeli subjects with an initial neoplastic finding in screening colonoscopy. The participants were followed over a period of 10 years, and underwent up to five surveillance colonoscopies. Clinical data regarding potential risk factors for colorectal cancer as well as blood samples were collected. Genetic polymorphisms were detected using real-time PCR from DNA extracted from peripheral mononuclear cells. Results: The overall prevalence of recurrent Colorectal carcinoma and adenoma was 9.4% (36/383) and 69% (268/383) respectively, with a median of 4.8 years from index colonoscopy. In a univariate analysis, subjects with recurrent lesions had significantly higher number of adenomas at index colonoscopy (3.9 Vs 1.1, p=0.001), increased rate of high grade dysplasia (65.8% Vs 50%, p=0.018), and a non-significant trend for larger adenomas and villous histology. The APC I1307K gene variant was detected in 11.8% of subjects with recurrent lesions compared to 3.8% of subjects with normal follow-up colonoscopies (p=0.03). In a multivariate logistic regression (adjusted to age, sex, family history of CR neoplasia, time to recurrence and number of colonoscopies performed), the I1307K variant and the presence of dysplasia were the only significant predictive factors for recurrent neoplasia with an OR of 3.27 (1-11.02, p=0.05) and 1.72 (1.02-2.89, p=0.04) respectively. Conclusions: The APC I1307K gene variant is an important predictive factor for recurrent colorectal neoplasia after a positive index colonoscopy and should be considered as part of the criteria for high risk subjects among Israeli Jews.