Polymorphisms in Phase I (CYP450) Genes CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP19A1 (rs749292) and CYP2C8 (rs1058930) and Their Relation to Risk of Breast Cancer: A Case-Control Study in Mazandaran Province in North of Iran

Abstract

BACKGROUND: The second leading cause of cancer-related death in women is breast cancer. Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. In the metabolism of xenobiotic, cytochrome P450s or monooxygenases perform an important function by catalysing the hydroxylation reaction. In this study, the susceptibility and genetic polymorphisms of CYP450 isoenzymes was investigated that may have an etiological role in breast cancer. AIM: The main purpose of this study was to evaluate the association of CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP2C8 (rs1058930), and CYP19A1 (rs749292) polymorphisms with the risk of breast cancer in Mazandaran province. MATERIAL AND METHODS: This cross-sectional case-control study were recruited 72 patients and 51 healthy individuals and was performed between March 2018 to May 2018 in the Oncology Department at Imam Hospital in Sari city, Iran. Peripheral blood samples were collected in EDTA tube, and DNA extraction was performed using the salting-out method and WizPrep extraction kits. Breast cancer patients with known clinicopathological characters and healthy women as control group were genotyped for genes polymorphisms by PCR-RFLP technique, using restriction enzymes. Chi-square, Fisher exact test and Logistic regression model, were applied for statistical analysis. RESULTS: The results of the experiments showed that there was a significant relationship between two groups and the age of the patients is significantly higher than the control group (p = 0.044). According to the chi-square and Fisher exact test, education, pregnancy, menopause status and oppose were significant between the two groups. Based on using a logistic regression model in two normalized and age-adjusted models to finding relationship between the genotypes of each gene and breast cancer risk, it was determined that in the CYP2C8 genotype, those who have the CG allele have a 7.74 degree increased risk of breast cancer (CI = 95% 0.95-62.5) and in the CYP19A1 gene, individuals with GA genotype, increased risk of breast cancer (CI = %95 1.52-27.21), about the CYP1B1 gene, people with two genotypes of CG + GG had higher risk of breast cancer (CI = %95 1.19-5.71) and allele G has decreased risk of breast cancer in this gene (P = 0.0271), also allele G in CYP2C8 gene had the protective effect (P = 0.02). In the age-adjusted model, for the CYP2C8 gene, GG genotype increased risk of breast cancer (CI = %95 1.11-75.84) as well as, the CG + GG genotype in CYP1B1 gene (CI = %95 1.31-6.57). CONCLUSION: Our results confirm the association between CYP2C8 (rs1058930), CYP19A1 (rs749292) and CYP1B1 (rs1056836) gene polymorphisms and increased risk of breast cancer in women in Mazandaran province.