NAT2 Fast Acetylator Genotype is Associated with an Increased Risk of Colorectal Cancer in Taiwan

Abstract

In Taiwan, colorectal cancer has one of the highest rates of increased incidence in the past two decades. Heterocyclic amines from dietary cooked meats are metabolically activated by NAT2 (N-acetyltransferase 2), which are associated with colorectal cancer incidence. Thus, the NAT2 fast acetylator genotype may be associated with colorectal cancer risk. However, the association between the NAT2 genotype and colorectal cancer risk is not clearly understood. We conducted a study with 244 primary colorectal cancer cases and 299 cancer-free healthy control subjects to verify the association of NAT2 polymorphisms with the risk of Taiwanese colorectal cancer. Our data showed that subjects with the NAT2 W/W homozygous genotype had a 1.63-fold increased risk of colorectal cancer compared with those with the Mx/Mx slow acetylator genotype (95 percent confidence interval, 1.03-2.58); however, no risk was found in the W/Mx heterozygous and Mx/W+W/W fast acetylator genotypes. Being stratified by gender factors, the colorectal cancer risk in females with homozygous W/W or Mx/W+W/W fast acetylators increased 2.47-fold and 2.13-fold compared with those with the Mx/Mx slow acetylator genotype (95 percent confidence interval, 1.27-4.82 for W/W genotype; 95 percent confidence interval, 1.17-3.89 for Mx/W+W/W genotype); however, the risk of the NAT2 genotype and colorectal cancer was not observed in males. Collectively, patients with the NAT2 fast acetylator genotype were more prone to colorectal cancer and reflected the possibility that exposure to heterocyclic amines may contribute to colorectal cancer development in Taiwan, especially in Taiwanese females.

NAT2 fast acetylator genotypes are associated with an increased risk for lung cancer with wildtype epidermal growth factor receptors in Taiwan

“…Although our results did not reveal the association of smoking with NAT2 fast acetylator likely due to small sample size, we noticed that smoking patients were slightly more likely to be NAT2 fast acetylators. One explanation for the association of NAT2 fast acetylator with wildtype EGFR might be that, in lung cancer, as well as in colon cancer, NAT2 might play a greater role in bioactivation than in detoxification [16,17]. Individuals with fast acetylator genotypes may be prone to heterocyclic aromatic amine-induced DNA damage, as a result of efficient activation of heterocyclic aromatic amine to reactive metabolites.…”

“…In fact, NAT2 acetylator genotypes have been implicated to be a risk factor for multiple cancers, including lung cancer [9][10][11]. Two groups have reported the association of lung cancer in female nonsmokers and NAT2 genotypes in ethnic Chinese population, albeit with different conclusions, suggesting that NAT2 genotypes might be a potential risk factor for this subpopulation of patients [16,17]. Since the distribution of NAT2 polymorphisms is highly ethnic-dependent, and both NAT2 genotypes and the presence of EGFR mutations are associated with lung cancer in Asian female nonsmokers, we hypothesized that NAT2 acetylator genotypes might represent a risk factor for NSCLC with EGFR mutations in Taiwanese population.…”

Polymorphism of N-acetyltransferase 2 Gene and the Susceptibility to Alcoholic Liver Cirrhosis: Interaction With Smoking

“…Appling this method to our data, we could find most of the genotypes performed by our method were still have 100 or near 100% probability to the actual genotypes. Some rare SNPs may have discrepancy between the data from PHASE reconstruction and actual genotypes, but these SNPs, other than SNP 481, 590, and 857, are very rare in Chinese (Garcia-Martin, 2008;Huang et al, 2007;Lin et al, 1994;Xie et al, 1997). To elucidate this ambiguity, we further check on the probability of haplotype using SAS ⁄ Genetics 9.1 statistical program.…”

“…Thirdly, difference in the frequency of NAT2 genotypes between Spaniards and Chinese may also attribute to the inconsistent results. (Lin et al, 1994) 18.0% (Huang et al, 2007) ALC, alcoholic liver cirrhosis; ANC, alcoholic noncirrhosis; SNP, single nucleotide polymorphism. Cigarette smoke contains thousands of chemicals, including highly reactive free radicals, which may cause oxidative stress (Arteel, 2003), and probably increases the risk of liver cirrhosis in patients with ALD, chronic hepatitis C, and primary biliary cirrhosis (Pessione et al, 2001;Yu et al, 1997;Zein et al, 2006).…”

GSTT1/GSTM1 Genotype and Anti-Tuberculosis Drug-Induced Hepatotoxicity in Peruvian Patients

“…Few studies have observed the relationship between GST genotypes and hepatotoxicity induced by antituberculosis drugs [ 12 , 15 , 32 ]. For example, Roy et al (2001) have observed a significant association between the GSTM1 homozygous null genotype and anti-tuberculous drug-induced hepatotoxicity in Indian tuberculosis patients.…”