Association of NAT2 phenotype with risk of head and neck carcinoma: A meta-analysis

Abstract

Abstract. N-acetyltransferase 2 (NAT2) is a key enzyme involved in the metabolism of xenobiotics and plays a significant role in the detoxification of numerous potential carcinogens. According to its acetylation status, NAT2 acetylator may be classified into two phenotypes, rapid and slow. Numerous studies have demonstrated that the polymorphisms of NAT2 were correlated with individual susceptibility to several malignant neoplasms, including head and neck carcinomas (HNC). However, the associations between the acetylator phenotypes and HNC risk in each study were not entirely consistent. To assess these associations more comprehensively, we performed a meta-analysis. In this meta-analysis, 16 eligible studies including 2,965 cases with HNC and 3,919 controls were identified by searching the databases of PubMed, Medline and the ISI Web of Knowledge. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to evaluate the association. No significant associations between the rapid acetylator phenotype in NAT2 and HNC risk were found either in the overall analysis (OR=0.98; 95% CI 0.83, 1.15; I 2 =57%; P heterogeneity =0.003) or in the subgroup analysis by ethnicity (for the Caucasian population, OR=1.03, 95% CI 0.85, 1.24, I 2 = 63%, P heterogeneity = 0.002; for other mixed populations, OR=0.78, 95% CI=0.61, 1.00, I 2 = 0%, P heterogeneity =0.47). In conclusion, this meta-analysis suggested that there is no association between the NAT2 phenotype and the risk of HNC. IntroductionHead and neck carcinoma (HNC), arising from the sites of the oral cavity, oropharynx, hypopharynx and larynx, is the sixth most common type of cancer worldwide (1). It is characterized by a moderately low survival rate, a high recurrence rate, and a high rate of second primary malignancy (2). In 2009, approximately 49,260 new cases (35,530 males and 13,730 females) of HNC were diagnosed in the USA, and 11,480 deaths occurred (8,300 males and 3,180 females) (1). Present evidence has proven that numerous factors contribute to the risk of squamous cell carcinoma of the head and neck, including tobacco use, alcohol consumption (3), viral infection (4) and genetic polymorphisms (5). In particular, tobacco smoking and alcohol consumption account for approximately 80% of HNC cases (6,7). However, it is worth noting that only a fraction of smokers and alcohol consumers develop HNC. This phenomenon suggests that host factors, including genetic variation, contribute to the inter-individual variation in the susceptibility to HNC.Numerous procarcinogens are known to exist in tobacco, including polycyclic aromatic hydrocarbons (PAHs), aromatic and heterocyclic amines; nitroso-compounds in smoking tobacco; and nitrosamines, aromatic and heterocyclic amines in smokeless tobacco. Most of these carcinogens generally undergo bioactivation and inactivation by phase Ⅰ and Ⅱ enzymes, respectively. The phase Ⅱ enzymes, including Glutathione S-transferases (GSTs) and N-acetyltransferase (NAT), contribute to the detoxification metabolism. Human NAT compr...

N-acetyltransferase 2: Slow, intermediate or fast? A booming question of the molecular epidemiology in cancer research

“…In the same way CRC along [80,106,[148][149][150][151][152][153][154][155][156][157][158], related to smoking and/or intake of red meat [123,125,129,130,149,[158][159][160][161] or cigarette smoking and prostate cancer [162]. The case of head and neck cancer, some studies also suggest an no significant difference in NAT2 slow, intermediate or fast acetylate [7,29,[72][73][74][75][76][77][78]163]. By analyzing a sample of American Caucasians, Chen, et al (2001) also showed that the risk of developing oral cancer is important, regardless of being fast, intermediate or slow acetylator individual, if the amount of cigarettes (>20 pack/years) or alcohol (>15 drinks/week) intake is high [164].…”

Association of N-acetyltransferase-2 polymorphism with an increased risk of coronary heart disease in a Chinese population

“…NAT2 alleles cause alterations in the enzyme activity; specifically, the rapid or slow acetylator phenotypes, arising from variations in the corresponding DNA sequences, have been correlated with changes in the enzyme activity and stability (Zheng et al, 2012). NAT2 plays a major role in isoniazid metabolism: the elimination rate of isoniazid is trimodally distributed, depending on the NAT2 phenotype (Kiyohara et al, 2009).…”

Association of N-acetyltransferases 1 and 2 Polymorphisms with Susceptibility to Head and Neck Cancers—A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis

“…Evidence from the published articles on the relationship between NAT1 and NAT2 polymorphisms and HNC susceptibility is conflicting [ 22 , 23 ]. The association between the polymorphisms ( NAT1 and NAT2 ) and the HNC risk has been evaluated by one [ 24 ] and four [ 25 , 26 , 27 , 28 ] meta-analyses, respectively. However, these studies were published several years ago with the most recent one being published in 2015.…”