NAT2, XRCC1 and hOGG1 polymorphisms, cigarette smoking, alcohol consumption and risk of upper aerodigestive tract cancer

Cintia Rodrigues Marques; Thiago Magalhães Da Silva; Dulcineia Martins De Albuquerque; Meiryane Santos Chaves; Marcilio Ferreira Marques Filho; Jamille Silva Oliveira; Giuliano Di Pietro; Sandra Mara Bispo Sousa; Aguinaldo Luiz Simões; Fabrício Rios-Santos

NAT2, XRCC1 and hOGG1 polymorphisms, cigarette smoking, alcohol consumption and risk of upper aerodigestive tract cancer

Anticancer Res. 2014 Jun;34(6):3217-24.

Affiliations

¹ Laboratory of Pharmacogenomics and Genetic Epidemiology (LAFEM), Department of Health, State University of Santa Cruz (UESC), Ilhéus, Brazil.
² Laboratory of Human Genetics, Department of Biology, State University of Southwest Bahia (UESB), Jequié, Brazil [email protected].
³ Hematology and Hemotherapy Center, University of Campinas (UNICAMP), Campinas, Brazil.
⁴ Laboratory of Genetics, Federal University of Sergipe (UFS), Lagarto, Brazil.
⁵ Department of Natural Sciences, State University of Southwest Bahia (UESB), Vitória da Conquista, Brazil.
⁶ Faculty of Medicine of Ribeirão Preto, University of São Paulo, Department of Genetics, Ribeirão Preto, Brazil.
⁷ Laboratory of Physiology, Faculty of Medicine, Federal University of Mato Grosso (UFMT), Cuiabá, Brazil.

PMID: 24922697

Abstract

Aim: To evaluate associations between polymorphisms of the N-acetyltransferase 2 (NAT2), human 8-oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing protein 1 (XRCC1) genes and risk of upper aerodigestive tract (UADT) cancer.

Patients and methods: A case-control study involving 117 cases and 224 controls was undertaken. The NAT2 gene polymorphisms were genotyped by automated sequencing and XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms were determined by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism (PCR-RFLP) methods.

Results: Slow metabolization phenotype was significantly associated as a risk factor for the development of UADT cancer (p=0.038). Furthermore, haplotype of slow metabolization was also associated with UADT cancer (p=0.014). The hOGG1 Ser326Cys polymorphism (CG or GG vs. CC genotypes) was shown as a protective factor against UADT cancer in moderate smokers (p=0.031). The XRCC1 Arg399Gln polymorphism (GA or AA vs. GG genotypes), in turn, was a protective factor against UADT cancer only among never-drinkers (p=0.048).

Conclusion: Interactions involving NAT2, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms may modulate the risk of UADT cancer in this population.

Keywords: DNA repair; UADT cancer; alcohol drinking; genetic epidemiology; smoking.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alcohol Drinking / epidemiology*
Arylamine N-Acetyltransferase / genetics*
Case-Control Studies
DNA / analysis
DNA Glycosylases / genetics*
DNA-Binding Proteins / genetics*
Female
Follow-Up Studies
Gastrointestinal Neoplasms / epidemiology*
Humans
Male
Middle Aged
Neoplasm Staging
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide*
Prognosis
Respiratory Tract Neoplasms / epidemiology*
Risk Factors
Smoking / epidemiology*
X-ray Repair Cross Complementing Protein 1

Substances

DNA-Binding Proteins
X-ray Repair Cross Complementing Protein 1
XRCC1 protein, human
DNA
Arylamine N-Acetyltransferase
NAT2 protein, human
DNA Glycosylases
oxoguanine glycosylase 1, human