No abstract

Breast carcinogenesis is a multistep process, involving both genetic and epigenetic modification process of genes, involved in diverse pathways ranging from DNA repair to metabolic processes. This study was undertaken to assess the role of promoter methylation of GSTP1 gene, a member of glutathione-S-transferase family of enzymes, in relation to its expression, polymorphism, and clinicopathological parameters. Tissue samples were taken from breast cancer patients and paired with their normal adjacent tissues. A total of 51 subjects were studied, in which the frequency of promoter methylation in cancerous tissue was 37.25% as against 11% in the normal tissues (p ≤ 0.001). The hypermethylated status of the gene was significantly associated with the loss of the protein expression (r = −0.449, p = 0.001, odds ratio = 7.42, 95% confidence interval = 2.05-26.92). Furthermore, when compared with the clinical parameters, the significant association was found between the promoter hypermethylation and lymph node metastasis (p ≤ 0.001), tumor stage (p = 0.039), tumor grade (p = 0.028), estrogen receptor status (p = 0.018), and progesterone receptor status (p = 0.046). Our study is the first of its kind in Kashmiri population, which indicates that GSTP1 shows aberrant methylation pattern in the breast cancer with the consequent loss in the protein expression. Furthermore, it also shows that the gene polymorphism (Ile105Val) at codon 105 is not related to the promoter methylation and two are the independent events in breast cancer development.

Coding polymorphisms in several DNA repair genes have been reported to affect the DNA repair capacity and are associated with genetic susceptibility to many human cancers, including gastric cancer. An understanding of these DNA repair gene polymorphisms might assess not only the risk of humans exposed to environmental carcinogens but also their responses to different therapeutical approaches, which target the DNA repair pathway. In the present study, polymorphic variants of two DNA repair genes, XRCC1 Arg399Gln and XPD Lys751Gln, were chosen to be studied in association with gastric cancer susceptibility in the Kashmiri population. A total of 180 confirmed cases of gastric cancer (GC) and 200 hospital-based controls from Government Shri Maharaja Hari Singh Hospital, Srinagar, were included in the study. The genotyping for XRCC1 and XPD genes was carried out by polymerase chain reaction-restriction fragment length polymorphism. We found that tobacco smoking is strongly associated with GC risk (OR = 25.65; 95% CI: 5.49–119.7). However, we did not find any association of polymorphism of XRCC1 Arg399Gln (OR = 1.56; 95% CI: 0.32–7.82) and XPD Lys751Gln (OR = 0.46; CI: 0.10–2.19) with GC risk in the study population. The combination of genotypes and gender stratification of XRCC1 and XPD genotypic frequency did not change the results. Consumption of large volumes of salt tea was also not associated with gastric cancer risk. Polymorphic variants of XRCC1 Arg399Gln and XPD Lys751Gln are not associated with the risk of gastric cancer in the Kashmiri population. However, replicative studies with larger sample size are needed to substantiate the findings.

SARS-CoV-2 virus, the main culprit for COVID-19 disaster, has triggered a gust of curiosity both in the mechanism of action of this infection as well as potential risk factors for disease generation and regimentation. The prime focus of the present review, which is basically a narrative one, is in utilizing the current concepts of vitamin D 3 as an agent with myriad functions, one of them being immunocompetence and a promising weapon for both innate and adaptive immunity against COVID-19 infection. Some of the manifestations of SARS-CoV-2 virus such as Acute Respiratory Distress Syndrome (ARDS) overlap with the pathophysiological effects that are overcome due to already established role of vitamin D 3 e.g., amelioration of cytokine outburst. Additionally, the cardiovascular complications due to COVID-19 infection may also be connected to vitamin D 3 levels and the activity of its active forms. Eventually, we summarise the clinical, observational and epidemiological data of the respiratory diseases including COVID-19 disease and try to bring its association with the potential role of vitamin D 3 , in particular, the activity of its active forms, circulating levels and its supplementation, against dissemination of this disease.

Coronary artery disease (CAD) is a clinical manifestation of atherosclerosis in the arteries supplying myocardium. Inflammation is the cornerstone in the development and progression of atherosclerosis. Amongst the various biomolecules tumour necrosis factor-a (TNF-a), interleukin-18 (IL-18) and interleukin-1b (IL-1b) build an inflammatory bionetwork in developing the disease. In this study we investigated the association of TNF-a SNPs [-308G/A (rs1800629), À1031T/C (rs1799964), À863C/A (rs1800630)]; IL-18 [-137G/C (rs187238)] and IL-1b SNPs [+3954C/T (rs1143634), À31C/T (rs1143627), and À511C/T (rs16944)] with coronary artery disease risk in Kashmiri population. A total of 200 cases and 260 controls were recruited in the study. Logistic regression analysis was done to investigate the association between SNPs and CAD risk. In case of TNF-a, the À308G/A-A/A and À863A/A showed an association with disease while À1031T/C was found to have an inverse relation. The IL-18-137G/C showed no statistically significant difference between controls and cases. For IL-1b the +3954C/T and À31C/T SNP variants showed no disease association while À511T/T showed significant association. Haplotypic analysis revealed the haplotype ATCGCC and GTACCTC to be associated with CAD risk and GTCGTTT, in particular, showing a profound association. Overall, our study suggests that TNF-a and IL-1b promoter polymorphisms may act as genetic risk factors in developing the coronary artery disease.