Promoter CpG island hypermethylation and down regulation of XRCC1 gene can augment in the gastric carcinogenesis events.

Gastric cancer (GC) is a multistep process characterized by a gradual accumulation of genetic and epigenetic alterations in genes at various stages of progression. Epigenetic alterations like DNA methylation play an important role in cancer and may serve as a biomarker for cancer. The present study was aimed to investigate the promoter hypermethylation, expression profile, and Arg399Gln gene polymorphism of DNA repair gene XRCC1 (X-ray repair cross complimentary group I) in GC patients. A total of 60 histopathologically confirmed GC subjects were recruited in the study. Information on various dietary, lifestyle and environmental factors was obtained in face-to-face interviews using a structured questionnaire from each subject. Tissue samples were taken along with adjacent non-cancerous tissues for analysis. Promoter methylation status and expression of XRCC1 gene was evaluated using MS-PCR and western blotting respectively; while as Arg399Gln polymorphism was analyzed by PCR-RFLP. We found that the XRCC1 gene promoter of 38.3% cancerous tissues were methylated compared to 13.3% of adjacent normal tissues. The promoter hypermethylation status of the gene was found to be significantly associated with the loss of protein expression (P < 0.0001, OR = 14.63; 95% CI 4.01-53.43). However, we did not find any significant association of polymorphism of XRCC1 Arg399Gln with promoter methylation or protein expression. Further, comparison of methylation status and protein expression with clinical parameters like age, smoking status, etc. was also not significant (P > 0.05). The present study indicates that XRCC1 undergoes aberrant promoter hypermethylation with subsequent loss of protein expression in gastric cancer.

Role of the Functional Polymorphism of Survivin Gene (-31G/C) and Risk of Breast Cancer in a North Indian Population.

INTRODUCTION: Survivin is an apoptosis inhibitor and plays a primary role in cancer development and progression. One of the most common polymorphism of the survivin promoter -31G/C (rs9904341) influences its expression and is associated with the risk of cancer development. This study was conducted to explore survivin promoter gene -31G/C (rs9904341) polymorphism and the risk of breast cancer. PATIENTS AND METHODS: The study group included 190 pathologically confirmed breast cancer patients, in addition to 200 distinct cancer-free controls from Jammu and Kashmir region of India, where breast cancer is the most common cancer in women. Single nucleotide polymorphism genotyping for -31G/C polymorphism in the survivin promoter region was done using a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The variant genotype/allele was found in 54.1% of the cases compared with 46.5% of controls. The combined prevalence of genotype GC+CC was significantly higher in patients compared with the control group (P = .02). Analyses of odds ratios (ORs) in the patient and control groups indicated that the presence of homozygous CC genotype was associated with increased risk for development of breast cancer (OR, 2.04; 95% confidence interval [CI], 1.07-2.98). The gene frequencies for G and C alleles were statistically different between patient and control groups (OR, 1.37; 95% CI, 1.03-1.84). CONCLUSION: The results suggest the association of -31G/C survivin polymorphism at a genotypic and allelic level in breast cancer.

Usefulness of pre- and post-operative calcium and Vitamin D supplementation in prevention of hypocalcemia after total thyroidectomy: A randomized controlled trial.

BACKGROUND: Total thyroidectomy (TT) is a commonly performed surgery and postoperative hypocalcemia is a major detriment to early discharge. The aim of this randomized controlled trial was to ascertain the usefulness of routine pre- and post-operative calcium and Vitamin D supplementation in prevention of hypocalcemia after TT. MATERIALS AND METHODS: Sixty consecutive patients who underwent total or near TT from February 2013 to August 2014 were included in the study. They were randomly divided into two groups - Group 1 received oral calcium (500 mg every 6 h) and Vitamin D (calcitriol 0.25 mcg every 6 h) 7 days before and 7 days after the surgery; and Group 2 did not receive supplementation. Symptoms and signs of hypocalcemia were monitored. Calcium profile was measured pre- and post-operatively at 6, 12, 24, 48, 72 h, and on 30th day. Hypocalcemia after surgery was either symptomatic or laboratory documented. Serum calcium level ≤ 8.5 mg/dl was considered as laboratory hypocalcemia. RESULTS: Twelve patients from Group 2, and 3 patients from Group 1 developed symptomatic hypocalcemia (P < 0.01). Laboratory hypocalcemia within postoperative 24 h was comparable between two groups, but more patients of Group 2 compared to Group 1 developed hypocalcemia at 48 h (6 and 13, respectively; P = 0.04) and at 72 h after surgery (5 and 14, respectively; P = 0.01). Twenty-four hours postoperative serum calcium level was significantly associated with grade of goiter, preoperative calcium, and nature of thyroid disease (benign or malignant). On multiple linear regression analysis, preoperative serum calcium was only independent variable significantly associated with development of 24 h post-TT hypocalcemia. CONCLUSION: Routine pre- and post-TT calcium and Vitamin D supplementation can significantly reduce postoperative hypocalcemia.

Clinical and laboratory profile of primary hyperparathyroidism in Kashmir Valley: A single-center experience.

BACKGROUND: Although primary hyperparathyroidism (PHPT) has become an asymptomatic disease in the West, in India, PHPT is still an uncommonly diagnosed, overtly symptomatic disease with skeletal, muscular, and renal manifestations. AIMS: To describe the profile and surgical outcome of 78 consecutive PHPT patients over a period of two decades at a single center. MATERIALS AND METHODS: All patients who underwent evaluation and surgery for PHPT from January 1996 to December 2015 were included. Evaluation included measurement of serum total calcium, inorganic phosphorus, alkaline phosphatase, intact parathyroid hormone, 25-hydroxy Vitamin D, 24 hour urinary calcium and radiological survey. Ultrasonography neck and technetium-99m sestamibi scan were used for preoperative localization. RESULTS: A total of 78 patients were identified during the two decades of whom 29 patients were studied retrospectively and 49 patients prospectively. Mean age of patients was 44.72 ± 12.46, and male:female ratio was 1:6. The most common presenting features were nephrolithiasis and/or nephrocalcinosis (64.10%), bone pain (44.1%), abdominal pain (39%), constipation (26%), and myopathy (14.10%). Fractures were present only in 10.25%, and brown tumors in 6.41% patients. The cure rate in our series was 96.15%. The mean parathyroid gland weight was 2.05 ± 3.03 g. None of the 41 patients in whom long-term follow-up was available, had recurrence of PHPT. CONCLUSIONS: The profile of PHPT is changing with older age at presentation, and emergence of renal stone disease and decline in overt skeletal disease as common presentation. The parathyroid weight in our study resembles that reported from developed countries.

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.

Gastric cancer in young patients.

AIM: The aim of this study was to see the clinical, pathological, and demographic profile of young patients with stomach carcinoma besides association with p53. PATIENTS AND METHODS: Prospective study of young patients with stomach carcinoma from January 2005 to December 2009. A total of 50 patients with age less than 40 years were studied. RESULTS: Male female ratio was 1 : 1.08 in young patients and 2.5 : 1 in older patients. A positive family history of stomach cancer in the first degree relatives was present in 10% of young patients. Resection was possible only in 50% young patients. 26% young patients underwent only palliative gastrojejunostomy. The most common operation was lower partial gastrectomy in 68%. Amongst the intraoperative findings peritoneal metastasis was seen in 17.4% in young patients. 50% young patients presented in stage IV as per AJCC classification (P value .004; sig.). None of the patients presented as stage 1 disease in young group. CONCLUSION: Early detection of stomach carcinoma is very important in all patients but in young patients it is of paramount importance.

The XRCC1 Arg399Gln gene polymorphism and risk of colorectal cancer: a study in Kashmir.

BACKGROUND: The DNA repair gene XRCC1 Arg399Gln gene polymorphism has been found to be implicated in the development of various cancers, including colorectal cancer (CRC), in different populations. We aimed to determine any association of this polymorphism with the risk of CRC in Kashmir. MATERIALS AND METHODS: A total of 120 confirmed cases of CRC and 146 healthy cancer free controls from the Kashmiri population were included in this study. Genotyping was carried out by the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Genotype frequencies of XRCC1 Arg399Gln observed in controls were 34.2%, 42.5% and 23.3% for GG (Arg/Arg), GA (Arg/Gln), AA( Gln/Gln), respectively, and 28.3%, 66.7% and 5% in cases, with an odds ratio (OR)=5.7 and 95% confidence interval (CI) =2.3-14.1 (p=0.0001). No significant association of Arg399Gln SNP with any clinicopathological parameters of CRC was found. CONCLUSIONS: We found the protective role of 399Gln allele against risk to the development of CRC. The XRCC1 heterozygote status appears to be a strong risk factor for CRC development in the Kashmiri population.

Long-term results of choledochoduodenostomy in benign biliary obstruction.

AIM: To determine the long-term results of choledochodudenostomy in patients with benign billiary obstruction. METHODS: This prospective study was conducted at Sheri Kashmir Institute of Medical Sciences Srinagar Kashmir, India over a period of 10 years from January 1997 to December 2007. The total number of patients who underwent choledochoduodenostomy during this period was 270. On the basis of etiology of biliary tract obstruction, patients were divided into a calculus group, an oriental cholangiohepatitis group, a benign biliary stricture group and others. Patients were followed for a variable period of 13 mo to 15 years. RESULTS: Choledochoduodenostomy (CDD) with duo-denotomy was performend in four patients. CDD with removal of T- tube, CDD with left hepatic lobectomy and CDD with removal of intra biliary ruptured hydatid was performed in three patients each. In the remaining patients only CDD was performed. Immediate post operative complications were seen in 63 (23%) patients, while long-term complications were seen in 28 (11%) patients, which were statistically significant. Three patients died during hospitalization while four patients died in the late post-operative period. CONCLUSION: Our conclusion is that CDD is safe and produces good long term results when a permanent biliary drainage procedure is required.

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.

Comparison of postoperative pulmonary function tests after cholecystectomy performed through Kocher's incision and mini-incision.

Comparative pulmonary function after cholecystectomy performed through Kocher's incision and mini-incision were evaluated. One hundred patients were included and systematically divided into two groups of 50 each. The first group underwent conventional cholecystectomy and the second group underwent mini-cholecystectomy. Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), and peak expiratory flow rate (PEFR) were determined on the preoperative day and on postoperative days 1, 2, and 3. The percentage of reduction of VC on postoperative day 1 (P < 0.01), 2 (P < 0.01), and 3 (P < 0.01) after Kocher's incision was more than the percentage of reduction after mini-incisions on the corresponding day, respectively (P < 0.01, P < 0.01, and P < 0.01). The percentage of reduction of FVC (P = 0.0001, 0.0001, and 0.0001) was lesser after mini-incision cholecystectomy than after Kocher's incision cholecystectomy on the three corresponding postoperative days. The percentage of reduction of FEV1 after mini-incision was lesser than after Kocher's incision cholecystectomy on the three corresponding postoperative days (P = 0.001, 0.000, and 0.000). There was no significant difference in PEFR between the two groups on the three corresponding postoperative days (P = 0.731, 0.652, and 0.393). It is observed that min-incision cholecystectomy is followed by superior postoperative pulmonary function to that seen after Kocher's incision.