The Influence of CYP3A4 Polymorphism in Sex Steroids as a Risk Factor for Breast Cancer

Abstract

Objective Epidemiological studies have shown evidence of the effect of sex hormones in the pathogenesis of breast cancer, and have suggested a relationship of the disease with variations in genes involved in estrogen synthesis and/or metabolism. The aim of the present study was to evaluate the association between the CYP3A4*1B gene polymorphism (rs2740574) and the risk of developing breast cancer. Methods In the present case-control study, the frequency of the CYP3A4*1B gene polymorphism was determined in 148 women with breast cancer and in 245 women without the disease. The DNA of the participants was extracted from plasma samples, and the gene was amplified by polymerase chain reaction. The presence of the polymorphism was determined using restriction enzymes. Results After adjusting for confounding variables, we have found that the polymorphism was not associated with the occurrence of breast cancer (odds ratio = 1.151; 95% confidence interval: 0.714–1.856; p = 0.564). We have also found no association with the presence of hormone receptors, with human epidermal growth factor receptor 2 (HER2) overexpression, or with the rate of tumor cell proliferation. Conclusion We have not observed a relationship between the CYP3A4*1B gene polymorphism and the occurrence of breast cancer.

Representation of CYP3A4, CYP3A5 and UGT1A4 Polymorphisms within Croatian Breast Cancer Patients’ Population

“…In comparison with the wild type CYP3A4*1A, CYP3A4*1B shows about a 2-fold increase in enzyme activity [15,16]. However, these data are not uniform, since a decrease in the catalytic activity of the enzyme was also determined [17], or unclear clinical effect was described [18], and some even linked this SNP with increased cancer risk [19,20]. Frequent single nucleotide polymorphism (SNP) of CYP3A5 gene is a substitution of adenine with guanine in intron 3: 6896A>G (rs776746).…”

Role of CYP3A4*1B Gene Variant In Substance Use Disorder

“…This functional variant, also known as CYP3A4*1B (rs2740574), is known to alter the gene's transcriptional activity and thus the overall activity of CYP3A4. It has been reported to reduce its activity (11). It has been reported that this activity change can lead to serious toxicity or therapeutic failure by altering the relationship between dose and blood concentration of the pharmacologically active drug by affecting the metabolic rate of drugs (10).…”