ABSTRACT
BACKGROUND: The Basque Country has one of the highest rates of head and neck squamous cell carcinoma (HNSCC) in Europe, although tobacco and alcohol consumption are not high when compared to other European countries where HNSCC incidence is lower. Our aim was to determine the role of genetic variation with regard to the metabolism of alcohol and carcinogens from tobacco smoke in the Basque Country. METHODS: Fourteen polymorphisms in alcohol or tobacco metabolism genes were genotyped in 84 HNSCC patients and 242 healthy individuals from the Basque Country. RESULTS: ADH1B histidine allele (rs1229984), CYP2E1 rs3813867 heterozygous genotype, and GSTT1 deletion conferred protection against HNSCC (OR: 0.318 [0.04-0.75], OR: 0.13 [0.02-0.94], and OR: 0.12 [0.02-0.60], respectively) while GSTP1 (rs1695) Val/Val genotype was related to an increased risk (OR: 4.12 [1.11-15.31]). Regarding alcohol and tobacco habits, GSTT1 deletion was associated with tobacco usage, while the 3 polymorphisms tested in ALDH2 were associated with alcohol consumption. However, genotypic distributions of these 7 SNPs did not differ from those observed for other Caucasian populations where HNSCC incidence is lower. CONCLUSIONS: The identified genotypic variations in alcohol and tobacco metabolizing genes only by themselves do not seem to be responsible for the higher incidence of HNSCC observed in the Basque Country.
Subject(s)
Alcohol Drinking/genetics , Carcinoma, Squamous Cell/genetics , Head and Neck Neoplasms/genetics , Smoking/genetics , Adult , Aged , Aged, 80 and over , Alcohol Dehydrogenase/genetics , Alcohol Dehydrogenase/metabolism , Alcohol Drinking/adverse effects , Alcohol Drinking/metabolism , Aldehyde Dehydrogenase/genetics , Aldehyde Dehydrogenase/metabolism , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/metabolism , Case-Control Studies , Female , Gene Deletion , Gene Frequency , Genetic Predisposition to Disease , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Head and Neck Neoplasms/etiology , Head and Neck Neoplasms/metabolism , Humans , Male , Middle Aged , Polymorphism, Genetic , Smoking/adverse effects , Smoking/metabolism , Spain , Squamous Cell Carcinoma of Head and NeckABSTRACT
Oral cancer is one of the most frequent head and neck cancers, and epidemiological studies have shown that smoking is a major risk factor in this pathology. However, as not all smokers develop oral cancer, some individuals must be more susceptible to develop this disease. This individual susceptibility has been related to different genetic variants in metabolizing enzymes. The cytochrome P-450 (CYP) family of enzymes metabolizes tobacco-related carcinogens producing reactive metabolites, which could cause DNA damage. Because of their functional role in the metabolism of tobacco-related compounds, the genetic polymorphisms found in the genes that code for CYP enzymes have been suggested to modulate oral cancer risk and contribute to individual susceptibility. In this review, we analyze and update the available evidence in the literature regarding the polymorphisms of CYP genes in relation to the susceptibility of developing oral cancer.
Subject(s)
Cytochrome P-450 Enzyme System/genetics , Mouth Neoplasms/enzymology , Polymorphism, Genetic/genetics , Carcinogens/metabolism , Genetic Predisposition to Disease/genetics , Humans , Mouth Neoplasms/genetics , Risk Factors , Smoking/geneticsABSTRACT
Oral and laryngeal cancer has a high incidence in the Basque Country (Spain), the main risk factors in this pathology being regular consumption of tobacco and alcohol. However, since not all the individuals exposed to these risk factors develop cancer, the individual genetic susceptibility should be investigated in this population. The aim of this study was to determine the distribution of alcohol dehydrogenase-1B polymorphism (Arg48His; rs1229984) in our region and analyze its association with the risk of oral and laryngeal squamous cell carcinoma. Samples from 87 patients with oral or laryngeal cancer and 242 healthy controls were analyzed. Multivariate logistic regression analysis showed that the combined Arg/His and His/His genotypes were associated with a reduced risk of head and neck squamous cell carcinoma (odds ratio: 0.203; 95% confidence interval: 0.052-0.796). In conclusion, the histidine allele was associated with a reduced risk of oral and laryngeal cancer in the Basque Country.
Subject(s)
Alcohol Dehydrogenase/genetics , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Laryngeal Neoplasms/enzymology , Laryngeal Neoplasms/genetics , Mouth Neoplasms/enzymology , Mouth Neoplasms/genetics , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/epidemiology , Case-Control Studies , Female , Genetic Predisposition to Disease , Humans , Laryngeal Neoplasms/epidemiology , Male , Middle Aged , Mouth Neoplasms/epidemiology , Polymorphism, Single Nucleotide , Spain/epidemiologyABSTRACT
Oral cancer is the sixth most common cancer worldwide and a major health problem in some parts of the world. Epidemiological studies have shown that habitual alcohol consumption could be a risk factor in oral carcinogenesis, although the true involvement of alcohol is unknown. Via alcohol dehydrogenase (ADH) and cytochrome P450 oxidase (CYP) alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Subsequently, and during the metabolizing process, acetaldehyde becomes acetate by acetaldehyde dehydrogenase (ALDH). Therefore, acetaldehyde levels are determined mainly by the action of ADH, CYP and ALDH. Recently, several studies have found that certain polymorphisms of genes encoding these enzymes confer a higher or lower metabolic activity and therefore different risk for certain malignancies such as oral cancer. In this review, we analyze the polymorphisms of alcohol metabolising enzymes in relation susceptibility to an oral cancer.
