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.

Genetic Factors of Idiopathic Gigantomastia: Clinical Implications of Aromatase and Progesterone Receptor Polymorphisms

“…On the other hand, authors from Iran found the association between CYP19A1 (rs749292) (also for CYP2C8 (rs1058930), CYP1B1 (rs1056836)) genes' polymorphisms and increased risk of breast cancer in women in Mazandaran province. G allele of rs749292 increased the risk of breast cancer [28]. Our analysis did not show differences between alleles' frequency of aromatase gene in women with gigantomastia and controls; however, in the case of CYP19A1 (rs749292), we found more frequent allele G in women with gigantomastia.…”

Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets

“…The CYP2C8 genotype (rs1058930), those who have the CG allele, have a 7.74 degree increased risk of breast cancer (CI = 95% 0.95–62.5) in women in Mazandaran province. 337 Moreover, the CYP2C8/9 *3/*1/*2/*1 genotype seem to be at higher risk of breast cancer recurrence (in tumors larger than 20 mm), especially in women treated with tamoxifen. 338 However, the most common functional genetic variant i.e.…”

Rat Mammary carcinoma susceptibility 3 (Mcs3) pleiotropy, socioenvironmental interaction, and comparative genomics with orthologous human 15q25.1-25.2

“…A majority of the rat-only genes encode olfactory receptors not conserved in the human genome. Eleven of the 23 genes in common had published associations with breast cancer ( Table 3 ) ( Kovacs 2001 ; Martinez et al 2008 ; Evensen et al 2013 ; Milke et al 2013 ; de Groot et al 2014 ; Tervasmäki et al 2014 ; Pangeni et al 2015 ; Sheng et al 2016 ; Kasoha et al 2017 ; Kalra et al 2018 ; Tolkach et al 2018 ; Chen et al 2019 ; Golmohammadzadeh et al 2019 ; Kønig et al 2019 ; Yu et al 2019 ).…”