Expression of genes related to iron homeostasis in breast cancer.

BACKGROUND: The dysfunctions in the metabolism of iron have an important role in many pathological conditions, ranging from disease with iron deposition to cancer. Studies on malignant diseases of the breast reported irregular expression in genes associated with iron metabolism. The variations are related to findings that have prognostic significance. This study evaluated the relationship of the expression levels of transferrin receptor 1 (TFRC), iron regulatory protein 1 (IRP1), hepcidin (HAMP), ferroportin 1 (FPN1), hemojuvelin (HFE2), matriptase 2 (TMPRSS6), and miR-122 genes in the normal and malignant tissues of breast cancer patients. METHODS & RESULTS: The normal and malignant tissues from 75 women with breast malignancies were used in this study. The patients did not receive any treatment previously. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used in figuring the levels of gene expression associated with iron metabolism. When the malignant and normal tissues gene expression levels were analyzed, expression of TFRC increased (1.586-fold); IRP1 (0.594 fold) and miR-122 (0.320 fold) expression decreased; HAMP, FPN1, HFE2, and TMPRSS6 expressions did not change. FPN1 and IRP1 had a positive association, and this association was statistically significant (r = 0.266; p = 0.022). IRP1 and miR-122 had a positive association, and this association had statistical significance (r = 0.231; p = 0.048). CONCLUSIONS: Our study portrayed the important association between genes involved in iron hemostasis and breast malignancy. The results could be used to establish new diagnostic techniques in the management of breast malignancies. The alterations in the metabolism of malignant breast cells with normal breast cells could be utilized to achieve advantages in treatment.

Association of XRCC3, XRCC4, BAX, and BCL-2 Polymorphisms with the Risk of Breast Cancer.

Background: Breast cancer is the most common malignancy in women. Genetic risk factors associated with breast cancer incidence have been identified. Aims: This study is aimed at determining the association of XRCC3 Thr241Met (rs861539), XRCC4 G(-1394) T (rs6869366) DNA repair and BAX G(-248) A (rs4645878), and BCL2 C(-938) A (rs2279115) apoptotic gene polymorphisms with breast cancer. Materials and Methods: Genetic analysis was performed using peripheral blood samples. Gene polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 175 patients and 158 healthy controls were enrolled in the study. Results: Breast cancer risk was 5.43 times more in individuals with AA genotype of Bax G(-248) A (rs4645878) (P = 0.002). The risk of metastasis was 11 times with this genotype. It was associated with 6 times more risk of having a tumor larger than 2 cm. The risk of breast cancer was 2.77 times more in individuals carrying the Met/Met genotype of XRCC3 Thr241Met (rs861539) (P = 0.009). The risk of having advanced clinical stage (stage III+IV) with the Met/Met genotype was 4 times more increased. No relationship with breast cancer was found with XRCC4 G(-1394) T (rs6869366) and BCL2 C(-938) A (rs2279115) gene polymorphisms. Conclusion: Multicenter trials using subjects with genetic variations are needed to establish the relationship between breast cancer and single gene polymorphism.

The role of TMPRSS6 gene variants in iron-related hematological parameters in Turkish patients with iron deficiency anemia.

TMPRSS6 gene mutations can result in iron deficiency anemia (IDA) and cause an increased iron-regulatory hormone, hepcidin, levels. TMPRSS6 encodes a serine protease, matriptase-2, which functions as negative regulatory protein of hepcidin transcription. Thus, TMPRSS6 variations might be risk factors for IDA. The aim of the study was to investigate the association of rs855791, rs4820268, rs5756506, rs2235324, rs2413450, rs2111833, rs228919, and rs733655 SNPs in TMPRSS6 gene with IDA susceptibility and iron-related clinical parameters. The study consisted of 150 IDA patients and 100 healthy controls. We analyzed the genotype distributions by using Real-Time polymerase chain reaction (Real-Time PCR) technique. We did not find any statistically differences for all SNPs between patients and controls (P > 0.05). In IDA patients, variations rs855791 and rs2413450 were associated with increased RBC (P = 0.03) and TIBC (P = 0.04), respectively. Also, increased of TIBC for rs4820268 (P < 0.05). On the other hand, in control group, rs5756506 was associated with two parameters, Hb (P = 0.02) and Hct (P = 0.03). We did not find markedly hepcidin levels in IDA patients compared to controls (P = 0.32). Our findings suggest that TMPRSS6 variations may not be risk factors for IDA. However, TMPRSS6 polymorphisms are associated with increased many iron-related hematological parameters.

Role of glutathione S-transferase M1, T1 and P1 gene polymorphisms in childhood acute lymphoblastic leukemia susceptibility in a Turkish population.

The variations between different individuals in the xenobiotic metabolizing enzymes' activity were shown to modify susceptibility to childhood acute lymphoblastic leukemia (ALL). Polymorphisms associated with genes coding for the glutathione S-transferase (GST) enzyme were known to affect the metabolism of different carcinogens. The aim of this study was to evaluate the influence of the GSTM1 and GSTT1 deletion polymorphisms, and the GSTP1 Ile105Val single nucleotide polymorphism (SNP) on the susceptibility to childhood ALL. The study was conducted in 95 children with ALL and 190 healthy control subjects from the Turkish population. The data revealed no difference in the prevalence of the GSTM1 and GSTT1 null genotypes between the childhood ALL patients and the controls. No association was found between GSTP1 Ile105Val variants and the susceptibility to childhood ALL, separately or in combination. Our findings suggested that the status of heritable GST polymorphism might not influence the risk of developing childhood ALL. Studies with a larger sample size are needed to evaluate and confirm the validity of our results.