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

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.

[1]  J. Little,et al.  N-acetyltransferase polymorphisms and colorectal cancer: a HuGE review. , 2000, American journal of epidemiology.

[2]  Jun Liu,et al.  HOGG 1 Ser 326 Cys Polymorphism and Susceptibility to Head and Neck Cancer : a Meta-analysis , 2012 .

[3]  J. Yokota,et al.  Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA , 1998, Oncogene.

[4]  L. Magno,et al.  Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations , 2010, BMC Genetics.

[5]  I. Kato,et al.  Alcohol in the aetiology of upper aerodigestive tract cancer. , 1994, European journal of cancer. Part B, Oral oncology.

[6]  P. Brennan,et al.  Influence of CYP1A1, CYP2E1, GSTM3 and NAT2 genetic polymorphisms in oral cancer susceptibility: results from a case-control study in Rio de Janeiro. , 2006, Oral oncology.

[7]  P. Porter,et al.  N-Acetyltransferase 2 polymorphisms, cigarette smoking and alcohol consumption, and oral squamous cell cancer risk. , 2001, Carcinogenesis.

[8]  D. Bell,et al.  Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. , 1995, Cancer research.

[9]  M. Romkes,et al.  Case–control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes , 2008, Head & neck.

[10]  E. Vokes,et al.  Expanding Role of the Medical Oncologist in the Management of Head and Neck Cancer , 2008, CA: a cancer journal for clinicians.

[11]  D. Hein Acetylator genotype and arylamine-induced carcinogenesis. , 1988, Biochimica et biophysica acta.

[12]  Y. Kuroda,et al.  DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population. , 2008, Japanese journal of clinical oncology.

[13]  Peter Dalgaard,et al.  R Development Core Team (2010): R: A language and environment for statistical computing , 2010 .

[14]  J. Brockmöller,et al.  Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer. , 1996, Cancer research.

[15]  M. Karagas,et al.  The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction. , 2002, Cancer research.

[16]  P. Chyou,et al.  Prospective study of the association of alcohol with cancer of the upper aerodigestive tract and other sites , 1992, Cancer Causes & Control.

[17]  P. Vineis,et al.  The Role of Genetically-based Metabolic Polymorphisms in Human Cancer : An Ecological Study of Bladded Cancer and N-Acetyltransferase in 23 Populations , 1998, Biotherapy.

[18]  A. Mitra,et al.  Protective association exhibited by the single nucleotide polymorphism (SNP) rs1052133 in the gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of squamous cell carcinomas of the head & neck (SCCHN) among north Indians , 2011, The Indian journal of medical research.

[19]  Laurent Excoffier,et al.  Arlequin (version 3.0): An integrated software package for population genetics data analysis , 2005, Evolutionary bioinformatics online.

[20]  D. Pang,et al.  The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis , 2010, Breast Cancer Research and Treatment.

[21]  D. Hein N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine. , 2009, Expert opinion on drug metabolism & toxicology.

[22]  J. Radicella,et al.  The human OGG1 gene: structure, functions, and its implication in the process of carcinogenesis. , 2000, Archives of biochemistry and biophysics.

[23]  Qi Song-tao,et al.  Association between the XRCC1 Arg399Gln Polymorphism and Risk of Cancer: Evidence from 297 Case–Control Studies , 2013, PloS one.

[24]  D. Grant,et al.  Pharmacogenetics of the arylamine N-acetyltransferases: a symposium in honor of Wendell W. Weber. , 2000, Drug metabolism and disposition: the biological fate of chemicals.

[25]  P. Brennan,et al.  Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review. , 2005, American journal of epidemiology.

[26]  M. Shriver,et al.  Ancestral proportions and their association with skin pigmentation and bone mineral density in Puerto Rican women from New York city , 2004, Human Genetics.

[27]  Shizhi Wang,et al.  The hOGG1 Ser326Cys polymorphism contributes to cancer susceptibility: evidence from 83 case-control studies. , 2012, Mutagenesis.

[28]  M. Rydzanicz,et al.  CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma. , 2005, Mutation research.

[29]  G. Williamson,et al.  ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL Radiology , 2014 .

[30]  F. Salzano,et al.  Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity , 2007, The Pharmacogenomics Journal.