Azra Shah

Association Between Copper Excess, Zinc Deficiency, and TP53 Mutations in Esophageal Squamous Cell Carcinoma From Kashmir Valley, India—A High Risk Area

Trace element deficiency or excess is implicated in the development or progression in some cancers. Here we report the elevated level of copper and low level of zinc in the plasma of esophageal cancer patients in Kashmir India—a high incidence area. The average level of copper was significantly higher (P < 0.0001) for patients than for controls, with a mean concentration of 169 μg/dl and 149 μg/dl for patients and controls, respectively. The control group consisted of 55 healthy individuals matched for age, sex, and place of residence of the patients. In contrast, the average level of zinc in patients was significantly lower than in controls (P < 0.0001), with a mean concentration of 86.8 μg/dl and 96.1 μg/dl for patients and controls, respectively. The levels of both copper and zinc showed significant differences based on gender and age in patients as compared to controls. Similarly, smokers depicted a significant increase in serum copper (N = 39, P = 0.002) and a decrease in serum zinc approaching level of significance in the patient group as compared to controls. The copper and zinc levels were significantly altered in patients (N = 40) when compared to controls as a function of snuff consumption. The differences in the levels of copper and zinc showed significant association with the consumption of local salted tea up to 1,500 ml per day, but the changes were insignificant beyond that. Patients with poorly differentiated tumors (N = 7) had a higher copper concentration than those with moderately or well-differentiated tumors (P < 0.0001). To validate the general notion that imbalance in copper and zinc levels may lead to higher prevalence of TP53 mutations, we compared the 3 variables, and no association was found between copper concentration and TP53 mutation status; but patients with TP53 mutant tumor had lower zinc levels than those with no mutation. In conclusion, our results point toward a role of the trace element imbalance in the esophageal tumorigenesis in high-risk Kashmiri population exposed to a range of nitroso compounds or their precursors. Further prospective cohort studies are warranted to determine whether change in the plasma zinc and copper homeostasis may represent an independent risk factor for this malignancy as well as a possible target for preventive intervention.

Lung cancer in the Kashmir valley.

Background: Lung cancer has been found to be the second commonest cancer according to a hospital-based data from Kashmir, India. However, no incidence studies are available. Objective: To ascertain the incidence of lung cancer in Kashmir. Materials and Methods: All newly histologically diagnosed cases of lung cancer seen in various hospital and private laboratories of the Kashmir valley were registered over a period of two years (January 1, 2004 to December 31, 2005). Also included were patients attending the various oncological service areas of the institute and those diagnosed from any other laboratory outside the state. The incidence rate was calculated using the January 2005 population as the reference population estimated using the census-based projected populations. Results: Four hundred and sixty–two incident cases of lung cancer were seen during the study period. The crude incidence rate, age standardized (world) and truncated age adjusted (40-69 years, world) incidence rates for lung cancer per 100 000 population were 4.01, 6.48 and 15.28 respectively (males 6.55, 10.09 and 23.94 respectively and females 1.19, 2.14 and 4.65). The age adjusted rates for males in district Srinagar was 19.34 per 100 000. One hundred and fifty nine (69.8%) of the 221 had a history of Hukkah smoking. Conclusions: Even though Kashmir as a whole is a low incidence area for lung cancer (ASR of < 15), Srinagar district has the highest incidence of lung cancer among the males in Kashmir. The data presented is assumed to be the closest approximation to a population-based data registry and the geographical incidence maps of ICMR need appropriate updating

Giant cell carcinoma of the lung.

A 50-year-old non-smoking, hypertensive female, presenting with superior vena caval compression, was found to have giant cell carcinoma of the lung. She received intensive combination chemotherapy. However she died in the following 36 hours, as a consequence of refractory hypotension.

CARCINOMA OF THE GASTROESOPHAGEAL JUNCTION ASSOCIATED WITH ADULT POLYCYSTIC KIDNEY DISEASE

This article is also accessible online at: http://BioMedNet.com/karger Dear Sir, Adult polycystic kidney disease (APKD) is the commonest heritable renal disorder, inherited as autosomal dominant trait with variable expressivity and nearly 100% penetrance. A hypervariable marker and a gene resulting in APKD are close enough on the short arm of chromosome 16 to be inherited in approximately 95% of the cases [1]. Both renal and extrarenal (gastrointestinal, cardiovascular, genitourinary and neurological) manifestations of APKD are known [2]. The occurrence of malignancy in this second most common inherited homogenic disease was no higher than the expected incidence in Germany. However, a report of pooled data revealed an incidence tenfold higher than that expected in the general population. Approximately 50% of the cases of renal neoplasias have been reported in APKD. The vast majority of patients have renal cell carcinoma, a few others having papillary carcinoma, transitional cell carcinoma and sarcoid varaint of renal cell carcinoma [3]. Cholangiocarcinoma is anecdotally reported as extrarenal complication of APKD. Herein, we report a family with APKD, having 2 members (brother and sister) developing adenocarcinoma of the gastroesophageal junction (fig. 1, 2). The brother, 40 years

Predominance of Central Asian and European families among Mycobacterium tuberculosis isolates in Kashmir Valley, India

BACKGROUND As there are no data available regarding the strains of Mycobacterium tuberculosis circulating in Kashmir Valley, India, the current study aimed at describing the genetic diversity of M. tuberculosis strains in this region, by spoligotyping and 12-locus-based MIRU-VNTR typing (Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat). METHODS Sputa from 207 smear positive cases with newly diagnosed pulmonary tuberculosis were subjected to culture for M. tuberculosis. Eighty-five isolates confirmed as M. tuberculosis were subjected to drug susceptibility testing and molecular typing by spoligotyping and MIRU-VNTRs. RESULTS Drug susceptibility results of 72 isolates revealed 76.3% as fully sensitive while 5.5% as multidrug resistant (MDR). Spoligotyping of 85 isolates detected 42 spoligotypes with 50 isolates (58.8%) clustered into seven spoligotypes. SIT26/CAS1_Del was the major spoligotype (23, 27%) followed by SIT127/H4 (12, 14.1%); CAS lineage (37.6%) was predominant, followed by Haarlem (25.8%) and ill-defined T clade (23.5%). MIRU-VNTR analysis displayed 82 MIRU patterns from 85 strains, including 3 small clusters and 79 unique. MIRU 26 was found to be the most discriminatory locus. CONCLUSIONS Kashmir Valley has CAS as the predominant lineage of M. tuberculosis similar to the rest of the Indian sub-continent, while it is peculiar in having Euro American lineages such as Haarlem and ill-defined T clade.