ABSTRACT
Vitamin D has a crucial role in cancer control and prevention. For its activity, VDR (vitamin D receptor) and its heterodimer RXR (Retinoid X receptor) are equally important in the cell. This ligand (vitamin D) and receptors (VDR-RXR) complex together triggers downstream DNA damage response in the cell and thus counters cancer in blood. 137 patients and 60 disease free controls were recruited for this study. The levels of vitamin D in patient and controls were analysed and compared using ELISA. The mRNA expression of the two receptor genes; VDR and RXR was also assessed by RT-PCR, to see their role in haematological malignancies. Their expression levels were corelated with the vitamin D levels in individuals to understand their mutual contribution in blood cancer prevention. The results confirmed a highly significant correlation between vitamin D levels of patients and controls (p < 0.001). The study also revealed that age of patients is a critical factor in determining the relative risk of blood cancer (p < 0.001), its types (leukaemia and lymphoma) and subtypes. Also, the mRNA expression of VDR showed a positive and non-significant relationship with vitamin D levels and RXR expression (p > 0.05). Based on our findings, and studies on other diseases it can be inferred that Vitamin D deficiency and dysregulation of its associated receptors may lead to cancer initiation and/or progression by failing to trigger the cellular DNA damage repair machinery.
Subject(s)
Gene Expression , Leukemia/blood , Leukemia/genetics , Lymphoma/blood , Lymphoma/genetics , RNA, Messenger/genetics , Receptors, Calcitriol/genetics , Retinoid X Receptors/genetics , Vitamin D Deficiency/blood , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , DNA Damage , DNA Repair , Female , Humans , Leukemia/complications , Lymphoma/complications , Male , Middle Aged , Receptors, Calcitriol/blood , Retinoid X Receptors/blood , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/complications , Young AdultABSTRACT
The main purpose of this study was to evaluate the association between reduction in XRCC2 gene and involvement of lymph node metastasis in breast cancer. In first part of the study, meta-analysis of 14 published XRCC2 studies was performed to define the role of XRCC2 gene as diagnostic marker and in second part of the study XRCC2 gene expression was observed using real time PCR in study cohort of 100 females (50 breast cancer patients and 50 controls). A statistically significant down regulation of XRCC2 (p < 0.04) and up-regulation of ki-67 (p < 0.05) was observed in breast cancer tissues compared to non-cancerous healthy tissues. In order to explore gene-gene and gene-clinicopathological parameters relationship Spearmen correlation was performed. We observed a significantly negative correlation between XRCC2 and Ki-67 expression (r = -0.376**, p < 0.01). In case of gene-clinicopathological parameters relationship, we observed a significant correlation between XRCC2 expression and lymph node status (r = -0.521***, p < 0.002) and metastatic status (r = -0.303*, p < 0.04) of breast cancer patients. Our data suggests that deregulation of XRCC2 in breast cancer has the potential to predict lymph node metastasis and may serve as a therapeutic target for breast cancer patients at risk of metastasis.
