Roohi Rasool

Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: A case control study.

The aim of this study was to investigate the role of the XRCC1 Arg399Gln polymorphism in the susceptibility of a Kashmiri population to colorectal cancer (CRC). We investigated the genotype distribution of the XRCC1 gene in 130 CRC cases in comparison with that of 150 healthy subjects. There was no direct significant association between the XRCC1 genotypes and CRC; however, the Arg/Gln genotype was associated with an elevated risk of CRC (OR>1.47) and the Gln/Gln variant genotype was associated with an increased risk of CRC in various clinicopathological parameters. This study suggests that the XRCC1 polymorphism is associated with an increased risk of CRC.

XRCC3 Thr241Met gene polymorphism and risk of colorectal cancer in Kashmir: a case control study.

XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC (p≤0.05). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p=0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.

Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal Cancer in Kashmiri Population: a Case Control Study.

BACKGROUND Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. MATERIALS AND METHODS In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. RESULTS Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p<0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. CONCLUSIONS Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.

Phytohemagglutinin-Induced Peripheral Blood Cytogenetics: A Valid Means for Diagnosis and Imatinib Therapy Monitoring of Chronic Phase Chronic Myeloid Leukemia Patients

Background: Conventional cytogenetic studies have been viewed as the standard follow-up method for Chronic Myeloid Leukemia patients on Imatinib. However, this approach is beset with high probability of poor metaphase index. In this study, we evaluated the application of Phytohemagglutinin (PHA)-induced peripheral blood culture based cytogenetic analysis (Karyotyping) in diagnosis and Imatinib treatment monitoring of the Chronic Phase CML patients. Methods: The patient samples were subjected to the PHA-induced peripheral blood culture based cytogenetic technique (Karyotyping) to establish their baseline cytogenetic status followed by their follow up Karyotyping twice at the end of 3 and 6 months of treatment. The simultaneous quantitative PCR (q-PCR) assay for BCR-ABL fusion gene transcript on the samples corresponding to their baseline as well as the follow up cytogenetic status was also carried out to authenticate the cytogenetic findings. Results: Complete Cytogenetic Response (CCR) and Partial Cytogenetic Response (PCR) was initially observed in 09 (30%) and 16 (53.3%) respectively of 30 CML patients with 05 (16.6%) patients showing no such response at the end of 3 months. At 6 months, 25 (83.3%) and 02 (6.6%) showed CCR and PCR respectively with 03 (10%) of patients without any response. The findings completely correlated with the hematological response, the q-PCR assay as well as the overall disease condition observed in the patients. Conclusion: As acquiring bone-marrow sample involves morbid consequences for patients and metaphases yielded thereby are difficult to analyze, PHA-induced peripheral blood Karyotyping was explored as an alternative. It was found to have significant potential in serving as a valid tool in the diagnosis and assessment of follow up response to Imatinib mesylate treatment of patients with chronic phase CML.

DNA Repair Gene - XRCC1 in Relation to Genome Instability and Role in Colorectal Carcinogenesis

Colorectal carcinogenesis is a multifactorial and multi-gene process, involving 3 major genetic instability pathways: chromosomal instability, microsatellite instability and CpG island methylator phenotype. Inefficient DNA repair is one of the causes of genetic instability leading to tumorigenesis. Defects in DNA repair genes are associated with cancer development. The XRCC1 gene is an important DNA repair genes and forms the component of several different damage recovery pathways, including base excision repair and single-strand breaks repair - the processes frequently involved in cancer transformation. In this review we have shed light on the structure and functioning of the XRCC1 gene and its protein, and the role played by XRCC1 in colorectal carcinogenesis.

Glutathione S Transferases: Biochemistry, Polymorphism and Role in Colorectal Carcinogenesis

Glutathione S-transferases (GSTs) are enzymes detoxifying a wide range of hazardous substances both of endogenous or exogenous origin, such as reactive oxygen species (ROS) or xenobiotics and environmental carcinogens; thereby imparting protection to DNA against oxidative damage. GST gene polymorphisms on the other hand, exert an effect on the functioning of enzymes encoded by these genes at both gene expression level and the activity of the protein. In this way it may influence the possibility of detoxification of carcinogens, and consequently, the level of DNA damage; thus it may have an effect on the risk of development of cancer. In this review we aim to understand the function of GSTs in the xenobiotic metabolism and their role in modulation of colorectal cancer (CRC).

SNP and Haplotype Analysis of Vascular Endothelial Growth Factor (VEGF) Gene in Lung Cancer Patients of Kashmir

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. In this large case-control study, we investigated whether functional polymorphisms (+405C>G, +936C>T) in the VEGF gene are associated with the risk of lung cancer. The study investigates the association between variants of VEGF gene and lung cancer. We performed single nucleotide polymorphism (SNP), haplotype and linkage disequilibrium studies on 100 patients and 128 healthy controls with 2 SNPs in the VEGF gene. The results were analyzed using logistic regression models, adjusted for age and sex. No Significant association was detected between individual SNPs and lung cancer using all the models of inheritance (codominant, dominant, recessive, over dominant and additive) for finding an association between genotypes and the cancer risk. The P values obtained for two markers were non-significant (P>0.05). Haplotype analysis produced additional support for the non-association of individual haplotypes/all haplotypes with the cancer risk (Global association P=0.56). Our findings suggest the non-involvement of genetic variants (+405C>G, +936C>T) of the VEGF gene in the etiology of lung cancer.

RAD51 G135C gene polymorphism and risk of colorectal cancer in Kashmir.

RAD51 – a DNA double-strand breaks repair gene plays an important role in homologous recombination, a process frequently involved in cancer transformation. The aim of this study was to compare the distribution of the genotype of the RAD51 G135C polymorphism between colorectal cancer (CRC) patients and controls. We also tested the association between the G135C polymorphism of the RAD51 gene and the risk of CRC, and various clinicopathological parameters. Polymorphism was evaluated by restriction fragment length polymorphism PCR in 100 CRC patients and 120 age-matched and sex-matched controls. There was a significant association between RAD51 genotypes and CRC cases (P<0.05). Also, the GC genotype was associated with an increased risk of CRC (odds ratio >3.84). Our results suggest that the G135C polymorphism of the RAD51 gene is associated with an increased risk of CRC in our population.

Correlation between Asthma Severity and Serum Vitamin D Levels: Experience from a Tertiary Care Centre in North India

Asthma is a chronic immunological disorder of the lungs characterized by reversible airway obstruction, airway inflammation, and increased airway hyper responsiveness in response to provocative challenges. Objective: The aim of this study is to assess the level of serum vitamin D in patients with bronchial asthma and its correlation with disease severity. Methods: The present study, included 120 patients diagnosed as bronchial asthma. The patients were grouped on the basis of vitamin D sufficiency and vitamin D levels were correlated with disease severity and lung function. Results: Vitamin D deficiency was highly prevalent in asthmatic patients, and there was a direct and a significant relationship between serum vitamin D levels, severity of asthma, control of asthma, serum IgE levels, sputum eosinophils and lung function. Conclusions: Measuring serum levels of vitamin D followed by supplementation could be considered in the routine assessment of patients with bronchial asthma.

Utility of procalcitonin in predicting mortality among cases of hospital-acquired pneumonia: a North Indian study

Bckground Data regarding the role of biomarkers like procalcitonin (PCT) in predicting treatment outcomes in hospital-acquired pneumonia (HAP) are limited in an Indian setting. We set out to determine the usefulness of PCT in predicting mortality among the cases of nosocomial pneumonia, at an 800-bed, apex tertiary care centre, in Kashmir (North India). Patients and methods Of the 318 confirmed cases of HAP, 60 consenting cases were selected randomly. Quantitative determination of PCT was done using immunofluorescence assays. Levels greater than 0.5 ng/ml were taken as positive. Data were collected on clinical parameters, and Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores pneumonia severity index were calculated. Appropriate blood and respiratory cultures were performed. Results Of the 60 cases included in the study, 19 (32%) died during the hospital stay, of which 14 (74%) deaths occurred in PCT-positive cases (P=0.001). The median PCT level was higher in the in-hospital mortality group (1.07 vs. 0.25), with a mean value of 1.2±2.8 vs. 1.2±2.5 in the group with no mortality (P=0.000). Using multivariate analysis, positive PCT level was strongly associated with in-hospital mortality (odds ratio: 6.767, 95%CI: 1.992–22.984, P=0.002) and APACHE-II score greater than 20 (n=14, odds ratio=4.5, 95%CI=1.448–13.984, P=0.009). Using receiver operating characteristic analysis, PCT had apropos discrimination power for in-hospital mortality (0.713 of area under the curve) and higher APACHE-II scores (0.753 of area under the curve). Using Cox regression model for mortality in PCT-positive group, the calculated hazard ratio was 3.273 (95%CI: 1.076–9.951, P=0.037). Conclusion PCT might have a vital role in the management of HAP, as a predictor of the poor treatment outcome.