N-Acetyltransferase 2 genetic polymorphisms and risk of colorectal cancer

World J Gastroenterol. 2011 Feb 14;17(6):760-5. doi: 10.3748/wjg.v17.i6.760.

Abstract

Aim: To investigate the possible association between meat intake, cigarette smoking and N-acetyltransferase 2 (NAT2) genetic polymorphisms on colorectal cancer (CRC) risk.

Methods: Patients with CRC were matched for gender and age to healthy controls. Meat intake and cigarette smoking were assessed using a specific frequency questionnaire. DNA was extracted from peripheral blood and the genotypes of the polymorphism were assessed by polymerase chain reaction-restriction fragment length polymorphism. Five NAT2 alleles were studied (WT, M1, M2, M3 and M4) using specific digestion enzymes.

Results: A total of 147 patients with colorectal cancer (76 women and 90 men with colon cancer) and 212 controls were studied. The mean age of the two groups was 62 years. More than half the subjects (59.8% in the case group and 51.9% in the control group) were NAT2 slow acetylators. The odds ratio for colorectal cancer was 1.38 (95% CI: 0.90-2.12) in slow acetylators. Although the number of women was small (n = 76 in the case group), the cancer risk was found to be lower in intermediate (W/Mx) acetylators [odds ratio (OR): 0.55, 95% confidence interval (95% CI): 0.29-1.02]. This difference was not observed in men (OR: 0.56, 95% CI: 0.16-2.00). Among NAT2 fast acetylators (W/W or W/Mx), meat consumption more than 3 times a week increased the risk of colorectal cancer (OR: 2.05, 95% CI: 1.01-4.16). In contrast, cigarette smoking increased the risk of CRC among slow acetylators (OR: 1.97, 95% CI: 1.02-3.79).

Conclusion: The risk of CRC was higher among fast acetylators who reported a higher meat intake. Slow NAT2 acetylation was associated with an increased risk of CRC.

Keywords: Colorectal cancer; N-acetyltransferase 2; Polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adult
  • Aged
  • Arylamine N-Acetyltransferase / genetics*
  • Case-Control Studies
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics*
  • Diet
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Meat
  • Middle Aged
  • Polymorphism, Genetic*
  • Risk Factors
  • Smoking
  • Surveys and Questionnaires

Substances

  • Arylamine N-Acetyltransferase
  • NAT2 protein, human