Study of the correlation between CYP1A1 gene promoter methylation and smoking in gastric cancer patients

Abstract

Background: Gastric cancer is one of the main causes of cancer related deaths particularly in northern parts of Iran. It has been recently attributed to the increased application of agricultural pesticides in these areas. CYP1A1 is the prototype member of the cytochrome P450 detoxifying enzymes that its gene expression alterations as a result of genetic or epigenetic changes, has been verified to have significant role on gastric cancer incidence. Materials and Methods: In this cross-sectional study, genomic DNA of tumoral and normal stomach tissues was extracted by phenol chloroform protocol and was subjected to bisulfite conversion by the EpiTech DNA Bisulfite kit. CpG-rich regions of the CYP1A1 gene promoter was amplified using specific primers and subsequently was sequenced in both directions using direct bisulfite Sanger sequencing method. Methylation rate of the individual CpGs was calculated and its correlation with demographic features was estimated by Spearman's test. Results: Results showed a significant positive correlation between promoter methylation of the CYP1A1 gene, particularly those CpGs existing in Xenobiotic response elements (XRE) consensus sequence, and smoking habit as well as familial history of gastric cancer. However, increasing age showed no significant effect on the methylation rate of the CYP1A1 gene promoter. Conclusion: Smoking and familial history of gastric cancer showed positive correlation with CYP1A1 gene promoter methylation. Screening of the CYP1A1 gene promoter methylation in smokers and individuals having positive familial history of disease may be used as a marker for gastric cancer diagnosis.

Keywords

• CYP1A1
• Methylation
• Gastric cancer
• Smoking tobacco