Brief Article
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World J Gastroenterol. Feb 14, 2011; 17(6): 760-765
Published online Feb 14, 2011. doi: 10.3748/wjg.v17.i6.760
N-Acetyltransferase 2 genetic polymorphisms and risk of colorectal cancer
Tiago Donizetti da Silva, Aledson Vitor Felipe, Jacqueline Miranda de Lima, Celina Tizuko Fujiyama Oshima, Nora Manoukian Forones
Tiago Donizetti da Silva, Aledson Vitor Felipe, Jacqueline Miranda de Lima, Nora Manoukian Forones, Oncology Group - Gastroenterology Division, Universidade Federal de São Paulo, 04023-900 São Paulo, Brazil
Celina Tizuko Fujiyama Oshima, Pathology Department, Universidade Federal de São Paulo, 04023-900 São Paulo, Brazil
Author contributions: Silva TD performed the majority of experiments; Felipe AV and de Lima JM were involved in editing the manuscript; Oshima CTF coordinated this work; Forones NM designed the study and ordinate this work.
Supported by The São Paulo Research Foundation (FAPESP), Oncology Group - Gastroenterology Division, Universidade Federal de São Paulo, São Paulo, Brazil
Correspondence to: Dr. Nora Manoukian Forones, Gastroenterology Division. Universidade Federal de São Paulo, R Botucatu 740 - 2º andar, 04023-900 São Paulo, Brazil. nora@gastro.epm.br
Telephone: +55-11-50841743 Fax: +55-11-50841743
Received: September 14, 2010
Revised: November 2, 2010
Accepted: November 9, 2010
Published online: February 14, 2011
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: N-acetyltransferase 2, Polymorphism, Colorectal cancer