CYP1A1, GSTM1 and GSTT1 polymorphisms, tobacco and alcohol status and risk of head and neck squamous cell carcinoma

Abstract

We examined the influence of the CYP1A1 A4889G and T6235C, GSTM1 and GSTT1 polymorphisms, involved in carcinogen metabolism, on the head and neck (HN) squamous cell carcinoma (SCC) risk. DNA from 142 HNSCC patients and 142 controls was analysed by polymerase chain reaction (PCR)-restriction fragment length polymorphism or multiplex-PCR for the polymorphisms analyses. Excesses of the CYP1A1 4889AG+GG and 4889AG+GG plus GSTT1 null genotype were seen in patients with heavy tobacco habit compared with controls (41.9% versus 26.8%, P = 0.03; 26.2% versus 10.3%, P = 0.04, respectively). Carriers of the referred genotypes and heavy tobacco consumption were under a 2.0-fold and 2.8-fold increased risks for HNSCC than others, respectively. The CYP1A1 6235TC+CC plus GSTM1 and GSTT1 null genotypes were more common in pharyngeal SCC patients than in controls (5.3% versus 0.7%, P = 0.04). Carriers of the combined genotype had 16.0-fold increased risk for the disease than others. The frequency of one null genotype of the GSTM1 or GSTT1 gene was higher in patients with pharyngeal SCC and heavy smoking status than in controls (76.3% versus 57.7%, P = 0.04). Carriers of the referred genotype and heavy tobacco status had a 2.4-fold increased risk for pharyngeal SCC than others. In contrast, the CYP1A1 6235TC+CC genotype was more common in controls than in laryngeal SCC patients (35.9% versus 21.6%, P = 0.01). Carriers of the genotype had a 0.2-fold decreased risk for the disease than others. Our data present preliminary evidence that inherited combined CYP1A1 A4889G and T6235C abnormalities and GSTM1 and GSTT1 pathways are important determinants of HNSCC, particularly pharyngeal SCC in heavy smoking individuals from south-eastern Brazil.

Gene‐environment interactions in determining differences in genetic susceptibility to cancer in subsites of the head and neck

“…An increased risk for malignancy in the oral cavity, pharynx, larynx was also observed among alcohol users in cases with variant CYP1A1, 1B1, 2E1 genotypes, or with the null GSTM1 genotype. This is consistent with previous reports indicating that alcohol is an independent risk factor for oral and pharyngeal cancers [Hung et al, 1997;Hashibe et al, 2007;Seitz and Stickel, 2007;Lourenco et al, 2011]. Quite similar risks for pharyngeal and laryngeal cancer were observed in alcohol users among cases with variant CYP1A1, 1B1, or 2E1 genotype or null genotypes of GSTM1, although the pharynx is the subsite within the head and neck that has been reported to show the highest sensitivity to the carcinogenic effects of alcohol [Blot et al, 1988;Hashibe et al, 2007].…”

Pharmacogenetics of drug metabolizing enzymes in Brazilian populations

“…The relationship of CYP1A1 and CYP1A2 variants with carcinogen exposure and cancer risk has been also evaluated by numerous studies in Brazilian cohorts [44][45][46][47][48], confirming an association of these genetic variants with cancer development in our population.…”

Association between Glutathione S-Transferase T1 Null Genotype and Gastric Cancer Risk: A Meta-Analysis of 48 Studies

“…Currently, GSTT1 null genotype has been proven to be associated with risks of some cancers, such as lung cancer and hepatocellular carcinoma [67], [68]. The significant associations further suggest that GSTT1 null genotype can affect the individual susceptibility to common malignancies, and has important roles the carcinogenesis of some cancers.…”