NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study

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dc.contributor.authorMatejcic, Marco
dc.contributor.authorVogelsang, Matjaz
dc.contributor.authorWang, Yabing
dc.contributor.authorParker, Iqbal M
dc.date.accessioned2015-07-30T04:12:28Z
dc.date.available2015-07-30T04:12:28Z
dc.date.issued2015-03-18
dc.date.updated2015-03-30T18:03:10Z
dc.description.abstractAbstract Background Tobacco 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. Methods Single 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. Results The 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). Conclusions Our 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.
dc.identifier.apacitationMatejcic, M., Vogelsang, M., Wang, Y., & Parker, I. M. (2015). NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study. <i>BMC Cancer</i>, http://hdl.handle.net/11427/13634en_ZA
dc.identifier.chicagocitationMatejcic, Marco, Matjaz Vogelsang, Yabing Wang, and Iqbal M Parker "NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study." <i>BMC Cancer</i> (2015) http://hdl.handle.net/11427/13634en_ZA
dc.identifier.citationMatejcic, M., Vogelsang, M., Wang, Y., & Parker, M. (2015). NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study. BMC cancer, 15(1), 150.
dc.identifier.ris TY - Journal Article AU - Matejcic, Marco AU - Vogelsang, Matjaz AU - Wang, Yabing AU - Parker, Iqbal M AB - Abstract Background Tobacco 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. Methods Single 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. Results The 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). Conclusions Our 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. DA - 2015-03-18 DB - OpenUCT DO - 10.1186/s12885-015-1105-4 DP - University of Cape Town J1 - BMC Cancer LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study TI - NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study UR - http://hdl.handle.net/11427/13634 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13634
dc.identifier.urihttp://dx.doi.org/10.1186/s12885-015-1105-4
dc.identifier.vancouvercitationMatejcic M, Vogelsang M, Wang Y, Parker IM. NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study. BMC Cancer. 2015; http://hdl.handle.net/11427/13634.en_ZA
dc.language.rfc3066en
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License*
dc.rights.holderMatejcic et al.; licensee BioMed Central.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0*
dc.sourceBMC Canceren_ZA
dc.source.urihttp://www.biomedcentral.com/bmccancer/
dc.subject.otherN-acetyltransferasesen_ZA
dc.subject.otherSingle nucleotide polymorphismen_ZA
dc.subject.otherAcetylator phenotypeen_ZA
dc.subject.otherEnvironmental carcinogensen_ZA
dc.subject.otherOesophageal canceren_ZA
dc.titleNAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study
dc.typeJournal Articleen_ZA
uct.type.filetype
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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