N-acetyl transferase 1: two polymorphisms in coding sequence identified in colorectal cancer patients

Area of Science:

• Genetics
• Molecular Biology
• Cancer Research

Background:

• Functional polymorphisms in N-acetyltransferase (NAT1 and NAT2) genes are associated with increased cancer risk.
• Investigating specific NAT1 gene polymorphisms in colorectal cancer (CRC) is crucial for understanding disease etiology.

Purpose of the Study:

• To identify and characterize NAT1 gene polymorphisms in colorectal cancer patients.
• To determine the frequency of these polymorphisms in CRC patients and controls.
• To explore potential associations between NAT1 polymorphisms, NAT2 genotypes, and colorectal cancer risk.

Main Methods:

• Heteroduplex analysis was used to detect NAT1 polymorphisms in CRC patients.
• DNA sequencing identified the wild-type NAT1*4 and two novel variants: NAT1*14 (C to T substitution) and NAT1*15 (G to A substitution).
• Allele and genotype frequencies were compared between 260 CRC patients and 323 Scottish controls.

Main Results:

• The NAT1*4 and NAT1*15 alleles were found at similar frequencies in both CRC patients and controls.
• The NAT1*14 allele was rare and exclusively found in the CRC group (0.006 frequency).
• NAT1*4/NAT1*15 genotype was less frequent in individuals with slow NAT2 genotypes, an association observed in both groups and deemed unrelated to cancer risk.

Conclusions:

• Coding region polymorphisms in the NAT1 gene are infrequent in the studied population.
• NAT1 gene polymorphisms do not appear to be independently associated with colorectal cancer risk.
• A non-random relationship between NAT1 and NAT2 polymorphisms suggests potential linkage between these enzymes.