Genetic polymorphism ofN-acetyltransferase 2 in the susceptibility to laryngeal squamous cell carcinoma

Department of Biochemistry, Mersin University, Zephyrium, Mersin, Turkey
Head & Neck (Impact Factor: 2.64). 01/2006; 27(12):1056-60. DOI: 10.1002/hed.20284
Source: PubMed


The purpose of this study was to investigate whether polymorphism of N-acetyltransferase 2 (NAT2) genotypes are associated with the risk of laryngeal squamous cell carcinoma (SCC).
The study group consisted of 45 white patients with laryngeal SCC (42 men, with a mean age of 54 years [range, 37-70 years] and three women, with a mean age of 47 years [range, 32-55 years]) and 104 control subjects (68 men and 36 women; mean age, 50 years; range, 28-73 years). All of the patients were primarily treated with surgical intervention. Blood samples (5 mL) were obtained before surgery or from the patients under follow-up to 5 years after surgery (mean follow-up, 27 months; range, 6-48 months). DNA was extracted from the lymphocytes by high pure template preparation kit. NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were detected by use of LightCycler-NAT2 mutation detection kit by real-time polymerase chain reaction with Light Cycler instruments. The association between NAT2 polymorphisms and laryngeal SCC was prospectively modeled through multivariate logistic regression analysis.
We found that the risk of laryngeal SCC was 7.3-fold higher in individuals with NAT2*5 mutant allele, 3.8-fold higher in subjects with NAT2*6 heterozygote allele, and 38.3-fold higher in NAT2*6 mutant allele. We also found that individuals with NAT2*7 heterozygote allele had a 0.2-fold less risk for the development of laryngeal SCC (p = .018).
In this population, patients with NAT2*5 mutant and *6 heterozygous and mutant genotypes had a significantly higher risk for development of laryngeal SCC.

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Available from: Yusuf Vayisoglu
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    • "With the step of screening the title or abstract, 11 eligible studies were selected (Boccia et al. 2008; Chatzimichalis et al. 2010; Drozdz et al. 1987; Gajecka et al. 2005; Henning et al. 1999; Jourenkova-Mironova et al. 1999; Lei et al. 2002; Morita et al. 1999; Rydzanicz et al. 2005; Unal et al. 2005; Varzim et al. 2002). Of the 11 articles selected, three studies by Boccia, Rydzanicz, and Unal (Boccia et al. 2008; Rydzanicz et al. 2005; Unal et al. 2005) were excluded because of the lack of data about acetylator status of laryngeal cancer and one study by Drozdz et al. (1987) was excluded because polymorphism was not determined by PCR-based method. Finally, seven studies including 980 laryngeal SCC cases and 1,487 controls were included in this meta-analysis based on inclusion and exclusion criteria (Table 1). "
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    ABSTRACT: N-acetyltransferase 2 (NAT2) plays an important role in the metabolism of various potential carcinogens, which can be subdivided into rapid and slow acetylation phenotype according to the different genotypes. A number of studies have been devoted to the association of NAT2 polymorphism with susceptibility to laryngeal carcinoma; however, the results were inconsistent and inconclusive. The aim of the present study was to conduct a meta-analysis assessing the possible association of NAT2 polymorphism with laryngeal cancer risk. The relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure until February 2011 and selected on the basis of the established inclusion criteria for publications, and then a meta-analysis was performed to quantitatively summarize the association of NAT2 polymorphism with laryngeal cancer susceptibility. Seven studies were included in the present meta-analysis, which described a total of 980 laryngeal cancer cases and 1,487 controls. The overall odds ratio (OR) for NAT2 slow and rapid acetylators was 0.99 (95% CI = 0.71-1.38) and 1.01 (95% CI = 0.72-1.40), respectively. When stratifying for race, the pooled ORs for NAT2 slow acetylator were 1.99 (95% CI = 1.10-3.63) in Asians and 0.85 (95% CI = 0.62-1.15) in Caucasians, and the pooled ORs for NAT2 rapid acetylator were 0.50 (95% CI = 0.28-0.91) in Asians and 1.18 (95% CI = 0.87-1.60) in Caucasians. This meta-analysis suggested that there was overall lack of association between NAT2 polymorphism and laryngeal cancer risk; however, NAT2 slow acetylation may contribute to a risk factor for laryngeal cancer in Asians but not in Caucasians.
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    ABSTRACT: The enzyme of N-acetyltransferase (NAT) is involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species (ROS). The excessive amount of ROS generation occurs in the ageing inner ear. The exact etiopathogenesis of presbycusis is not known, but it is generally accepted that it is the result of series of insults, such as physiologic age-related degeneration, noise exposure, medical disorders and their treatment, as well as hereditary susceptibility. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of NAT2 genotypes may be associated with the risk of presbycusis. Hospital-based, case-control study. We examined 68 adults with presbycusis and 98 healthy controls. DNA was extracted from whole blood, and the polymorphisms of NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. Gene polymorphisms at NAT2*5A, NAT2*7A/B, and NAT2*14A in subjects with presbycusis were not significantly different from in the controls (P > .05). However, in NAT2*6A, the risk of presbycusis was 15.2-fold more in individuals with mutant allele than subjects with wild genotype (P = .013). Individuals with NAT2*6A heterozygote allele had a 0.34-fold less risk in the development of presbycusis than subjects with mutant allele (P = .032) We demonstrated a significant association between the NAT2*6A polymorphism and age-related hearing loss in this population. However, the sample size was relatively small, and further studies need to investigate the exact role of NAT2 gene polymorphism in the etiopathogenesis of the presbycusis.
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    ABSTRACT: Polymorphisms at N-acetyl transferase 2 locus (NAT2) lead to slow, intermediate and rapid acetylation properties of the enzyme. Improper acetylation of heterocyclic and aromatic amines, present in tobacco, might cause DNA adduct formation. Generally, DNA repair enzymes remove these adduct to escape malignancy. But, tobacco users carrying susceptible NAT2 and DNA repair loci might be at risk of oral leukoplakia and cancer. In this study, 389 controls, 224 leukoplakia and 310 cancer patients were genotyped at 5 polymorphic sites on NAT2 and 3 polymorphic sites on each of XRCC1 and XPD loci by PCR-RFLP method to determine the risk of the diseases. None of the SNPs on these loci independently could modify the risk of the diseases in overall population but variant genotype (Gln/Gln) at codon 399 on XRCC1 and major genotype (Lys/Lys) at codon 751 on XPD were associated with increased risk of leukoplakia and cancer among slow acetylators, respectively (OR = 4.2, 95% CI = 1.2-15.0; OR = 1.6, 95% CI = 1.1-2.3, respectively). Variant genotype (Asn/Asn) at codon 312 on XPD was also associated with increased risk of cancer among rapid and intermediate acetylators (OR = 1.9, 95% CI = 1.2-2.9). Variant C-G-A haplotype at XRCC1 was associated with increased risk of leukoplakia (OR = 1.7, 95% CI = 1.2-2.4) but leukoplakia and cancer in mixed tobacco users (OR = 3.1, 95% CI = 1.4-7.1, OR = 2.4, 95% CI = 1.1-5.4, respectively) among slow acetylators. Although none of the 3 loci could modulate the risk of the diseases independently but 2 loci in combination, working in 2 different biochemical pathways, could do so in these patient populations.
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