Mutational analysis of the BRCA2 gene in breast carcinoma patients of Kashmiri descent.

Breast cancer demonstrates geographical and ethnic variation in its incidence reflecting the effect of local environmental conditions and lifestyle. The genesis of the disease has further been complexed by the involvement of a number of genes with small effects and above all by population heterogeneity. Accordingly, variations in genes, including breast cancer 1, early onset (BRCA1)/breast cancer 2, early onset (BRCA2), that have been markedly associated with the breast cancer phenotype exhibit a scattered mutational pattern in different populations. The present study was aimed to analyze the sequence variations in BRCA2 gene in a case control manner in ethnically pure Kashmiri population using PCR. Sequencing of BRCA2 exons revealed the presence of five sequence variations, four of which present in exon 11 alone were somatic and one was germline located in the U-terminal region (UTR) of exon 2. Out of these, the two somatic mutations comprised of substitutions, one representing a missense mutation leading to an amino-acid substitution at codon 991 and the other was a silent mutation at codon 1131, whereas the other two mutations located in exon 11 represented a loss of polymorphism. Codons for amino acid position 846 and 868 were demonstrated to be heterozygous polymorphic variants in 66% of the normal breast tissue samples, whereas the heterozygous polymorphic variant codons at the two loci were replaced by a homozygous genotype in associated tumor tissue in 88% of cases. These two mutations were always linked. Germline variation observed in exon 2 was located in the UTR region at contig position 13870572 (rs1799943). Other screened exons of BRCA2 did not demonstrate any sequence variation. These variations may contribute to breast cancer susceptibility along with variations in other low penetrating genes in sporadic types of breast cancer in this cohort of the population.

Epidemiological distribution and incidence of different cancers in Kashmir valley--2002-2006.

There are no population-based data available on cancer pattern in Kashmir and our study is the first kind which represents the trend in cancer pattern in the valley. The source of our data were cancer patients registered in the Department of Radiation Oncology, Sheri-Kashmir Institute of Medical Sciences, Srinagar, and Department of Radiation Oncology, SMHS, Srinagar during the period Jan 2002 to Dec 2006. These are leading medical centres in the valley and draw most all of cancer patients from all over Kashmir for treatment. During the period a total of 6,943 cases were registered of which 4,345 were males and 2,598 were females. The age standardized incidence rates were 34.9 per 100,000 for males and 24.8 per 100,000 for females. Oesophagus was the leading site of cancer in both sexes (male ASR 11.2; female ASR 8.3) followed by lung (ASR 6.5), brain (ASR 2.2) and head and neck (ASR 2.2) in males and breast (ASR 5.2), skin (ASR 1.6) and rectum (ASR 0.95) in females. The incidence of cervical cancer in females and prostate cancer in males was lower in Kashmir as compared to other Indian registries. Overall cancer incidence was significantly lower and cancer patterns were markedly different in Kashmir. The observed cancer pattern indicates that awareness campaigns, life style and dietary habit changes, tobacco-control measures and early detection of breast cancer are very important for cancer control in this population.

Reduced nitrate level in individuals with hypertension and diabetes.

BACKGROUND: Nitric oxide (NO) turnover is vital for proper endothelial function to maintain a healthy vascular system. Various risk factors responsible for hypertension and diabetes may disrupt this homeostasis, leading to decreased bioavailability and/or bioactivity of NO, which potentiates endothelial dysfunction. Plasma NO is a useful indicator of NO homeostasis and vascular endothelial function. Since endothelial function plays a key role in the development and progression of diseases like diabetes and hypertension, we sought to investigate the NO profile in patients having diabetes and hypertension and determine the relationship of NO turnover with the disease. MATERIALS AND METHODS: For this purpose, three groups were studied for the NO production. The first group consisted of 74 hypertensive patients, the second group consisted of 72 diabetic patients and the third group consisted of 60 healthy controls. Nitrate synthase activity was evaluated by measuring nitrate level using an automated sample injector connected to an automated NO detector - Ion liquid chromatograph. RESULTS: The plasma concentration of NO was found to be significantly lower in both essential hypertensive patients and diabetic patients without complications as compared to the healthy controls (P < 0.05). CONCLUSION: This data confirms that different factors like hyperglycemia and blood pressure are seen to have immense influence on NO production.