The Effect of N-acetyltransferase Polymorphisms, Diet and Smoking in the Aetiology of Adenomatous Polyps of the Left Colon

Chris Macklin

Aim:

To investigate the association of N-acetyltransferase 1 and 2 genotype and adenomatous polyps of the left colon and the interaction of these genes with diet and smoking on the polyp prevalence.

Methods:

The FlexiScope trial is a multicentre randomised controlled trial looking at the efficacy of a single flexible sigmoidoscopy and polypectomy as required at between the ages of 55 and 64 years in preventing colorectal cancer.  It is funded by the Imperial Cancer Research Fund and the Medical Research Council and has completed the screening phase of 40,000 people.  It has provided prospective recruitment of asymptomatic individuals either found at screening to have an adenomatous polyp of the left colon or found to be free of polyps.  Volunteers recruited from the FlexiScope trial completed dietary and smoking questionnaires and contributed blood for DNA analysis.  N-acetyltransferase (NAT) 1 and 2 genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism methods.  Analysis for associations between genotype, diet, smoking and adenomatous polyps were undertaken using chi-squared and regression analysis.  Sample size was increased by 3 centres collaborating on data collection.

Results:

887 matched cases and controls were recruited from the 3 collaborating centres.  Analysis for N-acetyltransferase genotype alone failed to show a significant association for either NAT1 or NAT2.  Smoking was confirmed as an independent risk factor for adenomatous polyps but N-acetyltransferase genotype did not influence this association.  Fast NAT1 genotype and a diet with high red meat content was associated with an increased risk of adenomatous polyps in the Leeds data (odds ratio = 3.37, 95% C.I. 1.31-8.69) but there was no consistent association for red meat consumption alone or in combination with NAT genotype in the collaborative data.

Conclusions:

There were no significant associations between NAT genotype, smoking, dietary consumption of red meat and adenomatous polyps of the left colon.