Tamoxifen Resistance and CYP2D6 Copy Numbers in Breast Cancer Patients

Abstract

Background: Breast cancer accounts about one million from total annual ten million new diagnosed cases of neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popular selective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Methods: This case control study was performed on samples taken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactions were conducted for 10 healthy samples using the comparative C t (Cycles threshold) method, each pair of genes being compared and samples with ratios around 1 were taken as control samples. Proliferation reactions were done by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program and analyzed. Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistant patients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitive patients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients with one and two copies was similar between two groups but patients with three copies were more likely to belong to the drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicating possible protective effects while that for three copies was 1.604. Conclusions: Based on our study there is no significant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer. But more studies considering other influencing factors appear warranted.

Micro-RNAs and Their Roles in Breast Cancer Pathogenesis; An Updated Review Article

“…34 Moreover, the inhibitory role of miR-31 on metastasis in breast cancer has been demonstrated in previous studies. 7 According to the results achieved in the presented studies, it seems that miRNAs b27, 31, 125, 141, 145, a2196, 200 family, 205, 206, 210, 429, and 499 along with let-7 are the molecules that have pre-apoptotic function and reduce the expression of oncogenic proteins and increase the expression of anti-apoptotic molecules. Accordingly, it may be concluded that the prevention of cancers such as breast cancer is plausible by increasing their expression.…”

“…7 Interestingly, these micro-molecules increase sharply in breast cancer and in addition to a vital role in making cells immortal, they are involved in metastasis and exacerbating the disease. 7 These miRNAs can be targeted in molecular therapies in breast cancer.…”

“…7 Interestingly, these micro-molecules increase sharply in breast cancer and in addition to a vital role in making cells immortal, they are involved in metastasis and exacerbating the disease. 7 These miRNAs can be targeted in molecular therapies in breast cancer. 7 For example, studies have shown that miR-21 is an oncogene in tumorigenesis, metastasis, and aggressiveness, and is associated with poor prognosis in breast cancer.…”

“…Recent research has shown that these molecules can act as either oncogenes or tumor suppressors. 6 Given the importance of etiology and treatment of tumors and due to many unknown causes of cancers, 7 extensive studies have discussed around the role of these micro molecules in the pathogenesis of cancers. Many studies have examined the possible molecules involved in cancer.…”

Digital PCR for determination of cytochrome P450 2D6 and sulfotransferase 1A1 gene copy number variations

“…On the other hand, investigations performed by Wegman P, et al (43) in Sweden and Okishiro M, et al (44) in Japan found no relationship of CYP2D6 or SULT1A1 genotypes with survival time. Similarly, Lum DWK, et al (45) analyzed the CYP2D6 genotype and tamoxifen response by meta-analysis, and found no association, while Motamedi S, et al (46) performed a study in Iran, and reported that there was no significant relationship between CYP2D6 copy number and tamoxifen resistance in their patients.…”