Genotype of Null Polymorphisms in Genes GSTM1, GSTT1, CYP1A1, and CYP1A1*2A (rs4646903 T>C)/CYP1A1*2C (rs1048943 A>G) in Patients with Larynx Cancer in Southeast Spain

Simple Summary Epidemiological studies have shown that individual susceptibility to cancer is mediated by genetic and environmental factors. The aim of the present study is to evaluate the individuals' metabolic genetic susceptibility to toxic habits (smoking and alcohol consumption) by detecting polymorphisms CYP1A1 rs1048943 T>C and CYPA1A2 rs4646903 A>G, and null polymorphisms in GSTM1 and GSTT1 genotypes, comparing a group of healthy control subjects with a population of larynx cancer patients from southeastern Spain. As results patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms. Background: some types of cancer have been associated with the presence of single nucleotide polymorphisms (SNPs) of some genes that encode enzymes: glutathione-S transferase (GST), whose alteration leads to loss of function and a lower capacity to eliminate toxic GSTM1 and GSTT1 null genotypes; SNPs causing loss of function of CYP1A1 or CYP1A1-2 cytochrome P450 enzymes related with a lower capacity to deactivate hydrocarbons related to smoking, which involves a higher risk of developing some smoking-dependent cancers including larynx cancer. Objective: to compare the presence of null SNPs in genes GSTM1, GSTT1, and CYP1A1 rs 4646903 T>C, and CYP1A1-2 RS1048943 A>G in patients with hypopharyngeal and larynx cancer with a healthy control group. Materials and method: The study included a total of 80 patients with hypopharyngeal and laryngeal cancer and 23 healthy subjects. Genomic DNA was obtained from saliva samples, determining genotype GSTM1 (present +, or null -), GSTT1 (present + or null -). Polymorphisms (SNP) in CYP1A1 T>C (present + CC, or absent - TC/TT), and CYP1A1-2 A>G (present + GG, or absent - AG/AA). Results: the mean age of patients with larynx cancer was 62 years and of control subjects 63 years. Of the total sample, over 95% were men, and over 90% were smokers. The presence of null genotypes for GTM1 was 50% in patients with larynx cancer (p= 0.042), while GSTT1 was 88.75% (p= 0.002). CYP1A1 rs4646903 T>C polymorphisms were detected in 100% of cases of larynx cancer and 17.39% of healthy subjects (p> 0.001). Conclusions: patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.