Gulzar Ahmad Bhat

Hookah smoking, nass chewing, and oesophageal squamous cell carcinoma in Kashmir, India

Background:Although cigarette smoking is an established risk factor for oesophageal squamous cell carcinoma (ESCC), there is little information about the association between other smoking and smokeless tobacco products, including hookah and nass, and ESCC risk. We conducted a case–control study in Kashmir Valley, India, where hookah smoking, nass chewing, and ESCC are common, to investigate the association of hookah smoking, nass use, and several other habits with ESCC.Methods:We recruited 702 histologically confirmed ESCC cases and 1663 hospital-based controls, individually matched to the cases for age, sex, and district of residence from September 2008 to January 2012. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).Results:Ever-hookah smoking (OR=1.85; 95% CI, 1.41–2.44) and nass chewing (OR=2.88; 95% CI, 2.06–4.04) were associated with ESCC risk. These associations were consistent across different measures of use, including intensity, duration, and cumulative amount of use, and after excluding ever users of the other product and cigarette smokers. Our results also suggest an increased risk of ESCC associated with ever-gutka chewing and -bidi smoking. However, the latter associations were based on small number of participants.Conclusion:This study shows that hookah and nass use are associated with ESCC risk. As prevalence of hookah use seems to be increasing among young people worldwide, these results may have relevance not only for the regions in which hookah use has been a traditional habit, but also for other regions, including western countries.

Socioeconomic status and esophageal squamous cell carcinoma risk in Kashmir, India

Studies have persistently associated esophageal squamous cell carcinoma (ESCC) risk with low socioeconomic status (SES), but this association is unexplored in Kashmir, an area with a high incidence of ESCC in the northernmost part of India. We carried out a case–control study to assess the association of multiple indicators of SES and ESCC risk in the Kashmir valley. A total number of 703 histologically confirmed ESCC cases and 1664 controls matched to the cases for age, sex, and district of residence were recruited from October 2008 to January 2012. Conditional logistic regression models were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals. Composite wealth scores were constructed based on the ownership of several appliances using multiple correspondence analyses. Higher education, living in a kiln brick or concrete house, use of liquefied petroleum gas and electricity for cooking, and higher wealth scores all showed an inverse association with ESCC risk. Compared to farmers, individuals who had government jobs or worked in the business sector were at lower risk of ESCC, but this association disappeared in fully adjusted models. Occupational strenuous physical activity was strongly associated with ESCC risk. In summary, we found a strong relationship of low SES and ESCC in Kashmir. The findings need to be studied further to understand the mechanisms through which such SES parameters increase ESCC risk.

Poor oral hygiene and risk of esophageal squamous cell carcinoma in Kashmir

Background:Several studies have suggested an association between poor oral health and esophageal squamous cell carcinoma (ESCC). We conducted a case-control study in Kashmir, a region with relatively high incidence of ESCC in north India, to investigate the association between oral hygiene and ESCC risk.Methods:We recruited 703 histologically confirmed ESCC cases, and 1664 controls individually matched to the cases for age, sex, and district of residence. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results:We found an inverse association between teeth cleaning and ESCC risk. As compared with never cleaning teeth, the OR (95% CI) was 0.41 (0.28–0.62) for cleaning less than daily and 0.44 (0.25–0.77) for cleaning at least once a day (P for trend=0.026) in models adjusted for multiple potential confounders, including several indicators of socioeconomic status. This association persisted after we limited our analyses to never tobacco users. The inverse association between cleaning teeth and ESCC was stronger with using brushes than with using sticks/fingers. We also found an association between the number of decayed, filled, and missing teeth and ESCC risk, but the trend of the associations was not statistically significant. Avoiding solid food and cold beverages because of teeth and oral problems were also associated with ESCC risk.Conclusion:We found an association between poor oral hygiene indicators and ESCC risk, supporting the previous studies that showed the same associations.

Polymorphic Variation in Glutathione-S-transferase Genes and Risk of Chronic Myeloid Leukaemia in the Kashmiri Population

Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ± S.D) 42.3 ± 13.4 years) and unrelated non-malignant controls (76 male and 48 females; age (mean ± S.D) 41.5 ± 12.9). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1 genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.

Salt tea consumption and esophageal cancer: A possible role of alkaline beverages in esophageal carcinogenesis

Salt tea is the most commonly used beverage in Kashmir, India, where esophageal squamous cell carcinoma (ESCC) is the most common cancer. Salt tea is brewed in a unique way in Kashmir, usually with addition of sodium bicarbonate, which makes salt tea alkaline. As little information about the association between salt tea drinking and ESCC was available, we conducted a large‐scale case‐control study to investigate this association in Kashmir. We recruited 703 histologically confirmed cases of ESCC and 1664 controls individually matched to cases for age, sex, and district of residence. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Participants who consumed >1,250 ml day−1 showed an increased risk of ESCC (OR = 2.60, 95% CIs = 1.68–4.02). Samovar (a special vessel for the beverage preparation) users (OR = 1.77, 95% CIs 1.25–2.50) and those who ate cereal paste with salt tea (OR = 2.14, 95% CIs = 1.55–2.94) or added bicarbonate sodium to salt tea (OR = 2.12, 95% CIs = 1.33–3.39) were at higher risk of ESCC than others. When analysis was limited to alkaline tea drinkers only, those who both consumed cereal paste with salt tea and used samovar vessel were at the highest risk (OR = 4.58, 95% CIs = 2.04–10.28). This study shows significant associations of salt tea drinking and some related habits with ESCC risk.

Promoter Methylation Status of DNA Repair Gene (hMLH1) in Gastric Carcinoma Patients of the Kashmir Valley

Cancer is a multi-factorial disease and variation in genetic susceptibility, due to inherited differences in the capacity to repair mismatches in the genome, is an important factor in the development of gastric cancer (GC), for example. Epigenetic changes, including aberrant methylation of 5/CpG islands in the promoter regions of mismatch repair (MMR) genes like hMLH1, have been implicated in the development of various types of GC. In the present study we evaluated the role of hMLH1 promoter hypermethylation in Kashmiri GC patients and controls, and assessed correlations with various dietary and lifestyle factors. The study included 70 GC patients (56 males and 14 females; age (mean ± S.D) 50 ± 11.4 years). Distinction between methylated and unmethylated was achieved with MS-PCR and DNA band patterns. The Chi-square test was applied to assess the risk due to promoter hypermethylation. We found a strikingly high frequency of promoter hypermethylation in GC cases than in normal samples (72.9% (51/70) in GC cases vs 20% (14/70) in normal samples (p=0.0001). We also observed a statistically significant association between methylated hMLH1 gene promoter and smoking, consumption of sundried vegetables and hot salted tea with the risk of GC. This study revealed that hMLH1 hypermethylation is strongly associated with GC and suggested roles for epigenetic changes in stomach cancer causation in the Kashmir valley.

Family history of cancer and the risk of squamous cell carcinoma of oesophagus: a case-control study in Kashmir, India.

Background:Only a few studies have examined the association between family history of cancer (FHC) and the risk of oesophageal squamous cell carcinoma (ESCC) in high incidence areas of ESCC. We conducted a case–control study to evaluate the relationship between FHC and ESCC risk in Kashmir, India, with analysis of detailed epidemiological data and information on multiple gene polymorphisms.Methods:We collected detailed information on FHC and a number of socio-demographic and lifestyle factors, and also obtained blood samples for genetic analysis from 703 histopathologically confirmed ESCC cases and 1664 individually matched controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).Results:Participants who had FHC showed a strong association with ESCC risk, and the risk was stronger when first-degree relatives (FDRs) had FHC (OR=6.8; 95% CI=4.6–9.9). Having a sibling with a cancer showed the strongest association (OR=10.8; 95% CI=6.0–19.3), but having a child with a cancer was not associated with ESCC risk. A history of any cancer in the spouse was also associated with ESCC risk (OR=4.1; 95% CI=1.6–10.2). Those with two or more relatives with FHC were at a higher risk of ESCC. After restricting FHC to familial ESCC only, the above associations were strengthened, except when spouses were affected with ESCC (OR=2.5; 95% CI=0.7–8.9). When we examined the associations between several single-nucleotide polymorphisms and ESCC in those with and without FHC, the associations of variant genotypes in cytochrome P450 (CYP) 2C19 and CYP2D6 and the wild genotype of CYP2E1 with ESCC were much stronger in those with FHC. The FHC had an additive interaction with several risk factors of ESCC in this population.Conclusion:Our results showed that FHC was strongly associated with ESCC risk in Kashmir. It seems both genetic factors and shared environment are involved in this association.

Contact with animals and risk of oesophageal squamous cell carcinoma: outcome of a case–control study from Kashmir, a high-risk region

Background Several studies have reported association between animal contact and some cancer types, including lymphohaematopoietic, colon, pancreatic and neurological malignancies. We aimed to investigate the association between animal contact and risk of oesophageal squamous cell carcinoma (ESCC) in a case–control study in Kashmir, India, area with a relatively high incidence of ESCC. Methods We recruited 703 histologically confirmed ESCC cases and 1664 controls individually matched to the cases for age, sex and district of residence. Information, including on animal contact, was obtained in face-to-face interviews using a structured questionnaire. Conditional logistic regression models were used to calculate ORs and 95% CIs. Results As compared with no contact with animals, daily close contact was associated with an increased risk of ESCC (OR 5.99; 95% CI 3.86 to 9.31) in models adjusted for several potential confounding factors, including multiple indicators of socioeconomic status. This association persisted in subgroups following stratification by a composite wealth score and occupation. Irregular contact with animals was not associated with ESCC risk. The association between duration of animal contact and ESCC risk was mixed; however, contact for more than 50 years was associated with an increased risk (OR 3.10; 95% CI 1.53 to 6.26). Frequency (p for trend, 0.001) and duration (p for trend, <0.001) of animal contact showed dose–response association with ESCC risk. Conclusions Our results suggest an association between long-term and daily close contact with animals and ESCC. This association needs to be investigated in further studies.

New phenolics from the root of Scutellaria prostrata JACQ. ex BENTH.

Scutellariaprostrata (Lamiaceae), a perennial herb growing as a lonely species in Kashmir, Himalayas, was subjected to repetitive column and flash chromatographic isolation for its chemical documentation-cum-bioevaluation. The methanolic extract of S.prostrata afforded the isolation of ten compounds (1–10), including two new compounds – scutellapbiflavanone (1) and scutellaprostin M (2). The known compounds were found to be scutellarin (3), hispidulin-7-O-β-d-glucopyranoside (4), baicalin (5), wogonoside (6), scutellaprostin C (7), acetoside (8), martynoside (9) and scutellaric acid-3-O-β-d-glucopyranoside (10). Isolation of biflavonoids, phenolics and phenylethanoid compounds from S.prostrata seals a deal of chemotaxonomic importance of this particular species. The characterisation of the compounds was achieved by 1H, 13C, 1H–1H DFQ COSY, HMBC, HSQC, HMQC and ROESY NMR experiments. All the compounds were tested for antioxidant, antimicrobial and cytotoxic activities.

Secondhand Smoking and the Risk of Esophageal Squamous Cell Carcinoma in a High Incidence Region, Kashmir, India: A Case-control–observational Study

AbstractStudies have associated secondhand smoking (SHS) with cancers of the lung, larynx, and pharynx. Only a few studies have examined the association between SHS and esophageal squamous cell carcinoma (ESCC) and the findings are inconclusive. We aimed to investigate the association between SHS and risk of ESCC in a case-control study in Kashmir, where the incidence of ESCC is high.We recruited 703 histopathologically confirmed ESCC cases and 1664 hospital-based controls individually matched to the cases for age, sex, and district of residence. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using conditional logistic regression models.Among never-tobacco users, the ORs for the association between SHS and ESCC risk were above unity with ever exposure to SHS (OR = 1.32; 95% CI, 0.43–4.02) and exposure to SHS for >14 h/wk (median value) (OR = 2.69; 95% CI, 0.75–20.65). In the analysis of data from all participants, the OR (95% CI) for the association between SHS and ESCC was (OR = 1.02; 95% CI, 0.53–1.93) for SHS ⩽14 h/wk and (OR = 1.91; 95% CI, 0.75–4.89) for SHS >14 h/wk in the models adjusted for tobacco use and several other potential confounding factors.We found an indication of increased risk of ESCC associated with exposure to SHS. Studies with larger numbers of SHS-exposed never tobacco users are required to further examine this association.