There is growing evidence of a malignancy-protective role for vitamin D in breast cancer. The effects of vitamin D are mediated via the vitamin D receptor (VDR) which is encoded by VDR gene. Several SNPs on VDR gene has attracted research interest, although the magnitude of the impact of VDR allelic variations on breast cancer has been controversial. In the present study, we focused on the distribution of VDR FokI and BsmI polymorphisms in Iranian breast cancer patients. A case-control study was conducted on 296 samples including 140 breast cancer patients and 156 age matched control women. Restriction fragment length polymorphism (RFLP) analysis was performed for BsmI and FokI genotyping. Randomly selected PCR products were subjected to sequencing to verify the RFLP results. A significantly increased risk of breast cancer was observed with BsmI bb or even Bb genotype (OR 2.39, CI 1.17-4.85 and OR 2.28, CI 1.16-4.47, respectively). Nevertheless, statistically significant association between FokI genotypes and breast cancer risk was not observed. This study lends support for an increased risk of breast cancer associated with the VDR BsmI polymorphism.

MicroRNA-34 family has anti-proliferative and apoptotic roles. Recent studies have shown that p53 upregulates miR-34 family leading to direct repression of several key oncogenes. Inactivation of miR-34a has been reported in multiple types of malignancies including breast cancer. The critical role of miR-34a in p53-mediated cell cycle arrest and apoptosis invokes studies focusing on the specific role of miR-34a dysregulation in carcinogenesis. While presence of p53 mutations has frequently been described in breast cancer, still most of the breast tumors do not show any variation in the p53 coding sequence or protein expression. Therefore, it is important to clarify possible involvement of other mediators of p53 pathway in breast cancer. In this study, expression of mature miR-34a in breast tumors with wild-type p53 was investigated in order to find any correlation between dysregulation of miR-34a expression and breast cancer. In about 40 % of the wild-type p53 samples, miR-34a was significantly downregulated. Neither hypermethylation of the miR-34a promoter nor genetic variations of the p53-binding site were detected in tumor samples with downregulated miR-34a. This study has provided evidence that miR-34a expression can be affected in a significant proportion of breast tumors independent of p53. Furthermore, downregulation of miR-34a was significantly associated with metastasis, while there was a significant correlation between upregulation of miR-34a and non-metastatic condition indicating a protective role for miR-34a against more invasive disease. Knowledge of miR-34a status may provide additional useful information regarding the nature of breast tumors, especially when p53 testing does not show any aberration.

BackgroundBreast cancer is the most common malignancy in women throughout the world. Mitochondria play important roles in cellular energy production, free radical generation and apoptosis. Identification of mitochondrial DNA mutations and/or polymorphisms as cancer biomarkers is rapidly developing in molecular oncology research.MethodsIn this study, the DNA alterations of the mitochondrial ATPase 6 and 8 genes were investigated in 49 breast cancer patients using PCR amplification and direct DNA sequencing on mtDNA. A possible association between these variants and tumorigenesis was assessed. Furthermore, the impact of non-synonymous substitutions on the amino acid sequence was evaluated using the PolyPhen-2 software.ResultsTwenty eight distinct somatic mitochondrial DNA variants were detected in tumor tissues but not in the corresponding adjacent non-tumor tissues. Among these variants, 9 were observed for the first time in breast cancer patients. The mtDNA variants of A8384 (T7A), T8567C (I14T), G8572A (G16S), A9041G (H172R) and G9055A (A177T) showed the most significant effects probably due to damaging changes to the resulting protein. Furthermore, non-synonymous amino acid changing variants were more frequent in the ATPase6 gene compared to the ATPase8 gene.ConclusionOur results showed that the ATPase6 gene is more susceptible to variations in breast cancer and may play an important role in tumorigenesis by changing the energy metabolism level in cancer cells.