Genomewide association analysis on green tea chemoprevention of colorectal adenoma: the importance of SLCO1A2 variants.

Abstract

Background: Green tea extract was tested for the secondary prevention of colorectal adenoma in the placebo-controlled MIRACLE trial. Genome-wide screening on adenoma recurrence was performed in n = 550 participants 3 years after randomization to green tea or placebo intake.

Methods: Single Marker Analysis followed by regression analyses was calculated for all 700.078 markers assuming an additive genetic model and including all covariates from the main MIRACLE trial analysis. The outcome was an adenoma rate at 3-year follow-up colonoscopy comparing participants carrying a genetic variant versus wildtype.

Results: The gene showing the strongest association with the outcome in both, SMA as well as regression analysis, was the organic anion transporter SLCO1A2. In the variant carriers, the adenoma frequency was 41.4% in the green tea group and 35.7% in the placebo group (RR 1.16 [0.81; 1.65] p = 0.61), whereas in the nonvariant carriers, the frequency of reoccurrence was 54.5% in the green tea group and 66.5% in the placebo group (RR 0.82 [0.69; 0.97], p = 0.03).

Conclusion: Individuals with genetic variants in the transporter SLCO1A2 may be protected against colon adenoma irrespective of the green tea intake. In nonvariant carriers of SLCO1A2, green tea was associated with a clear benefit in outcome (18% risk reduction).