Abstract
BackgroundTobacco smoking and red meat consumption are some of the known risk factors associated with the development of oesophageal cancer. N-acetytransferases (NAT1 and NAT2) play a key role in metabolism of carcinogenic arylamines present in tobacco smoke and overcooked red meat. We hypothesized that NAT1 and NAT2 genetic polymorphisms may influence the risk of oesophageal cancer upon exposure to environmental carcinogens.MethodsSingle nucleotide polymorphisms (SNPs) in the NAT1 and NAT2 genes were investigated by genotyping 732 cases and 768 healthy individuals from two South African populations to deduce the acetylator phenotype (slow, intermediate or rapid) from the combination of the genotyped SNPs.ResultsThe 341 CC genotype (rs1801280) was significantly associated with a reduced risk for oesophageal cancer in the Mixed Ancestry population (OR = 0.31; 95% CI 0.11-0.87). The NAT2 slow/intermediate acetylator status significantly increased the risk among cigarette smokers in the Black population (OR = 2.76; 95% CI 1.69-4.52), as well as among alcohol drinkers in the Mixed Ancestry population (OR = 2.77; 95% CI 1.38-5.58). Similarly, the NAT1 slow/intermediate acetylator status was a risk factor for tobacco smokers in the Black population (OR = 3.41; 95% CI 1.95-5.96) and for alcohol drinkers in the Mixed Ancestry population (OR = 3.41; 95% CI 1.70-6.81). In a case-only analysis, frequent red meat consumption was associated with a significantly increased cancer risk for NAT2 slow/intermediate acetylators in the Mixed Ancestry population (OR = 3.55; 95% CI 1.29-9.82; P = 0.019), whereas daily white meat intake was associated with an increased risk among NAT1 slow/intermediate acetylators in the Black population (OR = 1.82; 95% CI 1.09-3.04; P = 0.023).ConclusionsOur findings indicate that N-acetylation polymorphisms may modify the association between environmental risk factors and oesophageal cancer risk and that N-acetyltransferases may play a key role in detoxification of carcinogens. Prevention strategies in lifestyle and dietary habits may reduce the incidence of oesophageal cancer in high-risk populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1105-4) contains supplementary material, which is available to authorized users.
Highlights
Tobacco smoking and red meat consumption are some of the known risk factors associated with the development of oesophageal cancer
A number of epidemiological studies have pointed to tobacco smoking and alcohol consumption as major environmental risk factors for Oesophageal squamous cell carcinoma (OSCC) [4,5,6], and recent studies have reported a significant association between red meat intake and an increased risk of oesophageal cancer [7,8]
In the Mixed Ancestry group, the risk associated with tobacco smoking increased with the number of cigarettes smoked per day, with a 2.98-fold higher risk among those smoking
Summary
Tobacco smoking and red meat consumption are some of the known risk factors associated with the development of oesophageal cancer. A number of epidemiological studies have pointed to tobacco smoking and alcohol consumption as major environmental risk factors for OSCC [4,5,6], and recent studies have reported a significant association between red meat intake and an increased risk of oesophageal cancer [7,8]. Heterocyclic amines (HCAs) and nitrosamines are among the major arylamine carcinogens present in tobacco smoke and overcooked meat [9,10]. In humans these compounds are metabolized by the Phase I and Phase II xenobiotic metabolizing enzymes. The human NATs are encoded by two genes, NAT1 [HGNC:7645; Ensembl:ENSG00000171428] and NAT2 [HGNC:7646; Ensembl:ENSG00000156006], separated by 170 kb on chromosome 8p21.3 − 23.1 [12]
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