ASPO Abstracts
Genome-wide Association Study of Colorectal Adenoma Recurrence in the Selenium Trial
Category: Early Detection & Risk Prediction
Conference Year: 2020
Abstract Body:
Purpose of the Study: The purpose of this genome-wide association study was to identify genetic variants that are
associated with the risk of developing metachronous colorectal adenoma.
Methods: A total of 1,215 study participants of European descent from the Selenium Trial, a phase III, randomized,
double-blind, placebo-controlled clinical trial, were included. Participants in the Selenium Trial were between the
ages of 40 and 80 years and had complete removal of 1 or more colorectal adenoma within the 6 months before
study registration. The study included 534 cases with metachronous adenoma detected during three years of
follow up, and 681 controls without metachronous lesions. Logistic regression analyses adjusting for three
principal components, age, and sex were used to find genetic variants that were related to metachronous
adenoma risk.
Results: Our study identified variants in two independent loci that are suggestively associated with adenoma
recurrence (P<10-5). An intron variant of FAT atypical cadherin 3 in the FAT3 gene, rs61901554, showed the
strongest signal of association (P=1.10x10-6). The T allele was associated with increased odds of recurrence (OR
1.67; 95% Confidence Interval [CI], 1.36, 2.06). Two intron variants, rs12728998 and rs6699944, in NLRP3, a
gene encoding cryopyrin which forms inflammasomes, had the next strongest signal (P=2.00x10-6; OR, 1.68; 95%
CI, 1.36, 2.08). These two variants were in strong linkage disequilibrium (r2=1.0). The minor allele, T, of variant
rs6101554 was associated with multiple metachronous adenoma (OR, 1.46, 95% CI, 1.05, 2.04) and with
advanced metachronous adenoma (OR, 1.99, 95% CI 1.42, 2.80). Finally, the minor allele, A, of variant rs6699944
was also associated with the development of multiple metachronous adenoma (OR, 1.76, 95% CI, 1.27, 2.43) and
advanced metachronous adenoma (OR, 1.59, 95% CI 1.12, 2.28).
Conclusion: Our results provide new insight into the genetic basis of the development of metachronous colorectal
adenoma.
Keywords: Colorectal Cancer, Genome Wide Association Study, Metachronous Colorectal Adenoma