Towards a comprehensive understanding of the muscle proteome in Schizothorax labiatus: Insights from seasonal variations, metabolic responses, and reproductive signatures in the River Jhelum.

Proteomics is a very advanced technique used for defining correlations, compositions and activities of hundreds of proteins from organisms as well as effectively used in identifying particular proteins with varying peptide lengths and amino acid counts. In the present study, an endeavour has been put forth to create muscle proteome expression of snow trout, Schizothorax labiatus. Liquid chromatography-mass spectrometry (LC-MS) using label free quantification (LFQ) technique has extensively been carried out to explore changes in protein metabolism and its composition to discriminate across species, clarify functions and pinpoint protein biomarkers from organisms. In LFQ technique, the abundances of proteins are determined based on the signal intensities of their corresponding peptides in mass spectrometry. The main benefit of using this method is that it doesn't require pre-labelling proteins with isotopic tags, which streamlines the experimental procedure and gets rid of any bias that might have been caused by the labelling process. LFQ techniques frequently offer a wider dynamic range, making it possible to detect and quantify proteins over a broad range of abundances obtained from the complex biological materials including fish muscle. The results of proteomic analysis could provide an insight in understanding about how various proteins are expressed in response to environmental challenges. For proteomic study, two different weight groups of S. labiatus were taken from River Jhelum based on biological, physiological and logistical factors. These groups corresponded to different life stages, such as younger size and adults/brooders in order to capture potential variations in the muscle proteome related to growth and development. The proteomic analysis of S. labiatus depicted that an overall of 220 proteins in male and 228 in female fish of group 1 were noted. However, when male and female S. labiatus were examined based on spectral count and peptide abundance using ProteinLynx Global Software, a total of 10 downregulated and 32 upregulated proteins were found. In group 2 of S. labiatus, a total of 249 proteins in male and 301 in female fish were documented. When the two genders of S. labiatus were likened to one another by LFQ technique, a total of 41 downregulated and 06 upregulated proteins were identified. The variability in the protein numbers between two fish weight groups reflected biological differences, influenced by factors such as age, developmental stages, physiological condition and reproductive activities. During the study, it was observed that S. labiatus exhibited downregulated levels of proteins that were involved in feeding and growth. The contributing factors to this manifestation could be explained by lower feeding and metabolic activity of fish and decreased food availability during winter in River Jhelum. Contrarily, the fish immune response proteins were found to be significantly over-expressed in S. labiatus, indicating that the environment was more likely to undergo increased microbial infection, pollution load and anthropogenic activities. In addition, it was also discovered that there was an upregulated expression of the reproductive proteins in S. labiatus, which could be linked to the fish's pre-spawning time as the fish used in this study was collected in the winter season which is the pre-spawning period of the fish. Therefore, the present study would be useful in obtaining new insights regarding the molecular makeup of species, methods of adaptation and reactions to environmental stresses. This information contributes to our understanding of basic science and may have applications in environmental monitoring, conservation and preservation of fish species.

Carcinoma cervix: A single institute experience from Kashmir, Northern India.

Background: Carcinoma cervix is the fourth most commonly diagnosed cancer worldwide, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Carcinoma cervix is an uncommon malignancy in Kashmir. In this retrospective study, we have tried to find clinicopathological characteristics of carcinoma cervix along with the survival rates at our tertiary care hospital. Materials and Methods: Case records of cervical cancer patients registered from January 1, 2015, to January 1, 2019, were retrieved. A total of 138 patients was registered. 22 had undergone surgery, and out of these 17 had received postoperative radiotherapy. 109 patients were treated with definitive chemoradiation and 13 with palliative radiotherapy. Descriptive statistics were used to summarize patient and treatment-related variables, and Kaplan-Meier analysis was performed for survival analysis. Results: A total of 138 cases that were registered from 2015 to 2019 were included in this study. The median age at the presentation was 56 years. Most of the patients had a performance status of 1 (98 patients (71.01)). Most of the patients 110 (79.71%) were married before 20 years of age, only 1 patient was unmarried, and 85 (61.59) patients were multiparous in our study group. Only 14 (10.14%) patients in our study group had a history of oral contraceptive use and most of them were non-smokers [124 (89.80%)]. Multiple marriages were present in 8 (5.79%) patients only. The most common presenting symptom was bleeding per vagina (78.26%), and the maximum number of patients fall in the post-menopausal group (67.39%). 116 patients had squamous cell carcinoma histology while 10 patients had adenocarcinoma histology. Most of the patients had stage II and stage III disease (85 patients). At last, follow up out of 138 patients 75 (54.35) were alive. 3 year disease-free survival was 54.34% and 3-year overall survival was 72.46%. Conclusion: Carcinoma cervix is an uncommon malignancy in Kashmir because of different socio-cultural and religious practices but the response to treatment, toxicity profile, and survival are similar to the rest of the world.

Nosocomial SARS-COVID-19 Outbreak During the Third Wave of COVID-19 in an Oncology Facility at a Tertiary Care Hospital in Kashmir, India.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged as a life-threatening respiratory condition, especially in immunocompromised patients, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially detected in China in December 2019, the first case in India was diagnosed on January 30, 2020. Here we report a nosocomial COVID-19 outbreak among cancer patients and healthcare workers (HCWs) in a medical oncology unit of a tertiary care hospital from our region. MATERIALS AND METHODS: This was a descriptive study of the nosocomial COVID-19 outbreak and was conducted in the month of January 2022 at the medical oncology unit of a tertiary care hospital in Srinagar, Jammu and Kashmir (J&K), India. The study included 25 COVID-19 cases, including patients and HC/non-HCWs (NHCWs). The confirmation of diagnosis was done through real-time polymerase chain reaction (RT-PCR) using nasopharyngeal/oropharyngeal swabs as the test sample. RESULTS: Twenty-five COVID-19 cases, including 14 admitted patients, nine HCWs, and two NHCWs were confirmed by COVID-19 RT-PCR in a span of 11 days. The first case was a positive HCW. The patients were admitted for management of various hematological as well as solid organ malignancies. Of the 14 patients, eight were in the pediatric age group with a mean age of 6.9 years, and six were adults with a mean age of 55.2 years. Thirteen patients were on different chemotherapy protocols, and one was undergoing an autologous stem cell transplant. Of the 14 patients, four were asymptomatic for COVID-19 symptoms, eight had mild disease, and two had severe disease with respiratory failure. Two patients with severe diseases needed COVID-19-designated high-dependency unit (HDU) admission. There was one COVID-19-related death. Among the healthcare workers, the mean age was 33.8 years, of which six were males and three were females. All the HCWs and NHCWs had mild disease, and all of them recovered completely. CONCLUSION: Nosocomial COVID-19 illness is a new entity and is preventable. COVID-19 illness will remain in society after the pandemic is over, like the influenza B viral illness, and there can be seasonal flares in the future. Proper measures should be taken to prevent its clustering in hospital settings.

LC-MS/MS based characterisation and differential expression of proteins in Himalayan snow trout, Schizothorax labiatus using LFQ technique.

Molecular characterization of fish muscle proteins are nowadays considered as a key component to understand the role of specific proteins involved in various physiological and metabolic processes including their up and down regulation in the organisms. Coldwater fish specimens including snow trouts hold different types of proteins which help them to survive in highly diversified temperatures fluctuating from 0 to 20 °C. So, in current study, the liquid chromatography mass spectrometry using label free quantification technique has been used to investigate the muscle proteome profile of Schizothorax labiatus. For proteomic study, two weight groups of S. labiatus were taken from river Sindh. The proteomic analysis of group 1 revealed that a total of 235 proteins in male and 238 in female fish were recorded. However, when male and female S. labiatus were compared with each other on the basis of spectral count and abundance of peptides by ProteinLynx Global Server software, a total of 14 down-regulated and 22 up-regulated proteins were noted in this group. The highly down-regulated ones included homeodomain protein HoxA2b, retinol-binding protein 4, MHC class II beta chain and proopiomelanocortin while as the highly expressed up-regulated proteins comprised of gonadotropin I beta subunit, NADH dehydrogenase subunit 4, manganese superoxide dismutase, recombinase-activating protein 2, glycosyltransferase, chymotrypsin and cytochrome b. On the other hand, the proteomic characterisation of group 2 of S. labiatus revealed that a total of 227 proteins in male and 194 in female fish were recorded. When male and female S. labiatus were compared with each other by label free quantification, a total of 20 down-regulated and 18 up-regulated proteins were recorded. The down-regulated protein expression of group 2 comprised hepatic lipase, allograft inflammatory factor-1, NADH dehydrogenase subunit 4 and myostatin 1 while the highly expressed up-regulated proteins included glycogen synthase kinase-3 beta variant 2, glycogen synthase kinase-3 beta variant 5, cholecystokinin, glycogen synthase kinase-3 beta variant 3 and cytochrome b. Significant (P < 0.05) difference in the expression of down-regulated and up-regulated proteins was also noted between the two sexes of S. labiatus in each group. According to MS analysis, the proteins primarily concerned with the growth, skeletal muscle development and metabolism were down-regulated in river Sindh, which indicates that growth of fish during the season of collection i.e., winter was slow owing to less food availability, gonad development and low metabolic activity. While, the proteins related to immune response of fish were also noted to be down-regulated thereby signifying that the ecosystem has less pollution loads, microbial, pathogenic and anthropogenic activities. It was also found that the proteins involved in glycogen metabolism, reproductive and metabolic processes, particularly lipid metabolism were up-regulated in S. labiatus. The significant expression of these proteins may be connected to pre-spawning, gonad development and use of stored food as source of energy. The information generated in this study can be applied to future research aimed at enhancing food traceability, food safety, risk management and authenticity analysis.

Insights into molecular docking and dynamics to reveal therapeutic potential of natural compounds against P53 protein.

P53 is eminent tumour suppressor protein that plays a prominent role in cell cycle arrest, DNA repair, senescence, differentiation and initiation of apoptosis. P53 is an attractive drug target and the high toxicity of some cancer chemotherapy drugs increase the demand for new anti-cancer drugs from natural products. In this current scenario, identification of promising anticancer compounds from natural sources by repurposing approach is still relevant for the early prevention and effective management of cancer. In present study, we docked natural compounds like podophyllotoxin, quercetin and rutin along standard drugs (MG-132 and Bay 61-3606) against p53 protein. ADME/T analysis predicted toxicity of phytochemicals and drugs. In silico docking analysis of podophyllotoxin, quercetin and rutin gave HDOCK docking scores of -187.87, -148. 97 and -143.85, whereas control drugs MG-132 and Bay 61-3606 showed docking scores of -159.59 and -140.71 against p53 respectively. AutoDock analysis of rutin and MG-132 showed highest binding affinity scores of -7.3 and -6.8 kcal/mol against p53. Molecular dynamic simulation for p53 protein displayed stable conformation and convergence. In this study, P53-rutin complex showed free binding energy score of 11.84 kcal/mol and P53-MG-132 complex reported free energy score of 16.3 kcal/mol. Protein contacts atlas gives non-covalent contacts framework by exploring interfaces of individual subunits and protein-ligand interactions. STRING tool predicts physical and functional interactions between proteins. The results of this study revealed that rutin and MG-132 could be promising inhibitors against targeted p53 protein and this could prove detrimental for molecular therapeutics and drug-designing strategies.Communicated by Ramaswamy H. Sarma.

Patterns of Treatment and Outcomes in Epithelial Ovarian Cancer: A Retrospective North Indian Single-Institution Experience.

PURPOSE: Ovarian cancer (OC) is ranked as the third most common gynecologic cancer in various Indian cancer registries. In India, OC is seen in the younger age group, with a median age < 55 years being reported by most of the studies. The majority of patients are diagnosed in advanced stage (70%-80%), where the long-term (10-year) survival rate is poor, estimated at 15%-30%. The aim of this study was to evaluate clinical epidemiology, treatment patterns, and survival outcomes in patients with epithelial OC. METHODS: This was a retrospective analysis of patients with epithelial OC who were treated at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, over a period of 9 years, from January 2010 to December 2018. RESULTS: OC constituted 2.94% of all cancers registered. Epithelial OC constituted 88.4% of all OCs, with a median age 50 years. More than two third of patients belonged to rural background and the majority (76.9%) of the patients were in stage III or IV at the time of diagnosis. The main presenting symptoms were abdominal distension/bloating (46.5%) and gastrointestinal disturbances (35.2%). The most common histologic types were serous (65.9%) followed by mucinous carcinoma (15%). Median overall survival for the whole study cohort was 30 months (95% CI, 28.0 to 31.9). Median overall survival for stage I, II, III, and IV was 72, 60, 30, and 20 months, respectively. CONCLUSION: Most of the patients presented in advanced stage of the disease and have poor outcome. Delay in diagnosis and improper management before registering in tertiary cancer center and lack of tertiary care facilities are the root causes of poor outcomes. The general population and primary care physicians need to be made aware of OC symptoms.

The role of sex, season and reproduction status on blood parameters in snow trout (Schizothorax labiatus) from River Jhelum, Kashmir, India.

The current investigation was carried out with an aim to evaluate disparity in haematological and serum biochemical parameters of healthy male and female Schizothorax labiatus with respect to its four reproductive phases, i.e. preparatory (autumn), pre-spawning (winter), spawning (spring) and spent (summer). The study indicated that significant (p < 0.05) alterations were seen in gonadosomatic index (GSI) of S. labiatus with maximum value for both sexes noted in spring while minimum value in autumn. Contrary to this, the highest value of hepatosomatic index (HSI) for both sexes was noted in the autumn season and the lowest value in spring. The haemoglobin (Hb) content, red blood corpuscle (RBC) and white blood corpuscle (WBC) counts and haematocrit amount of S. labiatus also revealed significant (p < 0.05) variations with peak values noted in summer while least values were recorded during winter. It was also observed that male fishes comprised significantly (p < 0.05) maximum level of all these parameters amongst all seasons of the year, except WBC count. Erythrocyte indices specifically mean corpuscular haemoglobin (MCH), MCH concentration (MCHC) and mean corpuscular volume (MCV) exhibited insignificant (p > 0.05) alterations between the sexes. The lowest levels (p < 0.05) of serum glucose, cholesterol and urea were recorded in the pre-spawning period, i.e. winter, while as the highest values (p < 0.05) were seen in the summer because of the cessation of reproductive activities and greater availability of food. Similar trend was also noted in the amount of total protein, albumin and globulin of the fish, although insignificant (p > 0.05) variation was observed between sexes.

Parasitic anomalies observed in snow trout due to anthropogenic stress in water bodies.

There is interrelationship of the environmental conditions and fish health. Decrease or increase of pollution in aquatic ecosystem have direct impact on presence or absence of parasites. Fish living under optimum environmental, well-nourished conditions are more resistant to diseases than fish weakened by malnutrition caused by parasite infestation or due to deterioration of environmental conditions because ofpollution. Fish encounters common parasites in wild and in culture systems. Parasites attach to the host through suckers and hooks and make their way inside the host through different means, which include skin, through mouth along with food, by means of gills. The hosts were collected during Jan 2019 to Jan 2020 from river Veshaw. During this study it was observed that presence of parasites causes some changes in fish which can serve as indicators of deterioration in aquatic habitat. Clinical signs were noticed in fish hosts collected from sites which received waste due to anthropogenic activities. Parasitic anomalies in the host collected from polluted site was observed to include body deformaties, gastric distention, lesions in gut, increased mucus production, damage in gill filaments etc.

Clinical outcome of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy in locally advanced nasopharyngeal carcinoma: Comparative study at SKIMS Tertiary Care Institute.

Background: The management of nasopharyngeal cancer (NPC) at present is based primarily on radiotherapy, but the technique by which radiation therapy is delivered is different such as intensity-modulated radiotherapy (IMRT) and two-dimensional conventional radiotherapy (2D-CRT). Materials and Methods: In our study, IMRT and 2D-CRT were compared for their treatment outcome in locally advanced nasopharyngeal carcinoma (NPC) patients. Patients with Stage II to IVA nasopharyngeal cancer (NPC) as per the American Joint Committee on Cancer 7th and 8th edition 2017 treated with IMRT (n = 30) and 2D-CRT (n = 30) between October 2016 and October 2020 were retrospectively analyzed. We matched our patients by using the propensity-score matching method. OS was the primary endpoint of our study. The secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). Acute and late radiation toxicities between IMRT and 2D-CRT were also compared. Results: In the propensity-matched cohort of 60 patients, 30 patients received 2D-CRT and 30 patients received IMRT. Compared with the treatment of 2D-CRT, the IMRT group is associated with a better 3-year OS (70% vs. 85% P = 0.045), LRFS (78% vs. 96% P = 0.047), RRFS (78% vs. 95% P = 0.015), DFS (80% vs. 95% P = 0.034), and PFS (84% vs. 90% P = 0.024), while as DMFS (85% vs. 85% P = 0.147) were comparable in both the groups. IMRT was also associated with a lower incidence of late toxicities such as xerostomia and trismus. Conclusion: Our study demonstrates that IMRT yields better long-term overall survival and local control including LRFS, RRFS, DFS, and PFS. In addition, late toxicities induced by irradiation in nasopharyngeal carcinoma (NPC) are lower with IMRT. IMRT may be an effective treatment in nasopharyngeal cancer (NPC) as compared to 2D-CRT, but further studies are needed to establish the association.

ABO Blood Group and the Risk of Esophageal Squamous Cell Carcinoma in Kashmir, a High Risk Region.

BACKGROUND: ABO blood group has been linked with a number of diseases including cancer. Association of ABO blood type with esophageal squamous cell carcinoma (ESCC) has been sparsely reported and the results are inconsistent. We undertook this study to analyze if any association exists between the ABO and Rh blood groups and ESCC risk. METHODS: We conducted a hospital-based case control study to analyze ABO and Rh blood groups in patients with histologically proven diagnosis of ESCC and compared them with healthy donors from the same population. ABO and Rh blood group status of general population was obtained from the blood bank at Sher-i-Kashmir Institute of Medical Sciences (SKIMS) and from original articles published from time to time. Chi-Square test was performed to look for statistical significance. RESULTS: For this study, 206 patients were prospectively enrolled. Seventy-four (35.9%) patients had blood group O. Blood groups type A and type B was found each in 59 (28.6%) patients. In 108,014 healthy donors, 35.3% had blood type O followed by type B (33.66%). There was no significant difference in any of the blood types between patients with ESCC and donors (P = 0.31). CONCLUSION: No association exists between ABO blood type and the risk of ESCC.

Association of Activity Altering Genotypes - Tyr113His and His139Arg in Microsomal Epoxide Hydrolase Enzyme with Esophageal Squamous Cell Carcinoma.

The study aimed to explore the relationship of microsomal epoxide hydrolase (mEH) exon 3 (Tyr113His) and exon 4 (His139Arg) polymorphisms and predicted mEH activity with esophageal squamous cell carcinoma (ESCC) risk. 482 histologically confirmed cases and equal number of matched controls were analyzed by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). Conditional logistic regression models were used to examine the association of polymorphisms with ESCC. We noted exon 3 slow genotype (OR = 6.57; CI 3.43-12.57) as well as predicted low mEH activity (OR = 3.99; CI 2.32-6.85) was associated with the ESCC risk. Elevated ESCC risk estimates were seen in smokers independent of genotypes but the association was stronger among smokers with exon 3 variant (OR = 6.67; 3.29-13.53) and low activity (OR = 7.52; CI 3.46-16.37) genotypes. Positive family history of cancer synergistically increased ESCC risk in the individuals who harbored exon 3 (OR = 13.59; CI 5.63-32.81) or altered mEH activity genotypes (OR = 13.35; CI 5.10-34.94). Significant interaction was seen between mEH exon 3 and exon 4 genotypes (P = 0.006) and between predicted mEH activity and positive family history of cancer (P = 0.018). These findings suggest association of ESCC risk with mEH polymorphisms which get modified by tobacco smoking and positive family history of cancer.

CYP1A2*1F Gene Variant, Alkaline Salt Tea Intake and Risk of Esophageal Squamous Cell Carcinoma.

Unlike many other cancers, the relationship of CYP1A2*1F (rs762551) polymorphism with esophageal squamous cell carcinoma (ESCC) risk has not been assessed so far. To evaluate its association with ESCC, we conducted a case control study in Kashmir, India, a high risk region. We recruited 404 histopathologically confirmed ESCC cases and 404 controls, individually matched for sex, age and residence to the respective cases. Information was obtained on dietary, lifestyle and environmental factors in face to face interviews using a structured questionnaire from each subject. Genotypes were analyzed by polymerase chain reaction, restriction fragment length polymorphism and sequencing randomly selected samples. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that mutant genotype (AA) of CYP1A2*1F polymorphism was associated with ESCC risk (OR = 3.11; 95% CI: 1.72-5.36). A very strong ESCC risk was observed in subjects who drank >1250 ml of salt tea daily and harbored mutant genotype of CYP1A2*1F (OR = 14.51; 95% CI: 5.33-39.47). The study indicates that CYP1A2*1F polymorphism is associated with ESCC risk and the risk is modified in salt drinkers. However, more replicative and mechanistic studies are needed to substantiate the findings.

Association of Genetic Variants of CYP2C19 and CYP2D6 with Esophageal Squamous Cell Carcinoma Risk in Northern India, Kashmir.

Genetic polymorphism in xenobiotic metabolizing enzymes (XMEs) is associated with various malignancies. However, the association of esophageal cancer with XMEs is mixed. The current study was aimed to explore the association of genetic polymorphisms of cytochrome (CYP) 2C19 and CYP2D6 genotypes with esophageal squamous cell carcinoma (ESCC) risk in Kashmir, India. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing methods were used for genotyping of 492 ESCC cases and equal number of individually matched controls. Conditional logistic regression models were used to assess odds ratios (ORs) and 95% confidence intervals. Increased ESCC risk was observed in subjects with variant genotypes of CYP2C19 (OR = 3.3) or CYP2D6 (OR = 2.1) and risk was higher (OR = 4.6) in subjects who harbored both the genotypes. Almost same but higher risk turned when subjects were smokers and carried a variant genotype of CYP2C19 (OR = 4.4) or CYP2D6 (OR = 4.7). Risk was appreciably increased in subjects who had family history of any cancer and also harbored a variant genotype of either CYP2C19 (OR = 15.5) or CYP2D6 (OR = 9.7). Subjects harboring a variant genotype of CYP2D6 showed an added risk when they used biomass as fuel (OR = 4.6). In conclusion, variant genotypes of CYP2C19 and CYP2D6 are associated with an increased risk of ESCC.

Polymorphism of Metastasis Suppressor Genes MKK4 and NME1 in Kashmiri Patients with Breast Cancer.

Genetic polymorphisms in metastatic suppressor genes like MKK4 and NME1 are not well studied in breast cancer. Hence, we analyzed the relationship between MKK4 and NME1 polymorphisms and breast cancer risk in Kashmir, India. The different genotypes of NME1 and MKK4 genes were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 130 breast cancer cases and 200 age- and sex-matched controls. Conditional logistic regression models were used to assess the association of various genotypes with breast cancer. In this study, we found an inverse association between MKK4 promoter polymorphism and breast cancer risk. As compared to TT (wild) genotype, individuals with TG (heterozygous) (OR = 0.32; 95% CI = (0.17-0.58) and GG (mutant) (OR = 0.13; CI = 0.04-0.40) genotypes showed decreased risk of breast cancer. When participants were classified on the basis of lymph node involvement, a strong association between NME1 heterozygous genotype (OR = 3.82; CI = (1.54-9.44) and breast cancer was found.

Potential risk of esophageal squamous cell carcinoma due to nucleotide excision repair XPA and XPC gene variants and their interaction among themselves and with environmental factors.

The association of nucleotide excision repair (NER) gene polymorphisms with esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of the current study was to assess the association of repair gene xeroderma pigmentosum A (XPA) (rs-1800975) and xeroderma pigmentosum C (XPC) (rs-2228000) polymorphisms with ESCC risk as well as modifying effects of environmental factors. The genotyping was done in 450 confirmed ESCC cases and equal number of individually matched controls by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. Conditional logistic regression models were used to assess the genotypic associations and interactions. A high ESCC risk was found in subjects who carried the homozygous minor allele of XPA (odds ratio (OR) = 3.57; 95 % confidence interval (CI) = 1.76-7.23), and the risk was higher when analysis was limited to participants who were ever smokers (OR = 4.22; 95 % CI = 2.01-8.88), lived in adobe houses (OR = 8.42; 95 % CI = 3.74-18.95), consumed large volumes of salt tea (OR = 7.42; 95 % CI = 3.30-16.69), or had a positive family history of cancer (FHC) (OR = 9.47; 95 % CI = 4.67-19.20). In case of XPC, a homozygous minor allele also showed strong association with ESCC risk (OR = 4.43; 95 % CI = 2.41-8.16). We again observed a very strong effect of the above environmental factors in elevating the risk of ESCC. Further, the variant genotypes of both genes in combination showed an increased risk towards ESCC (OR = 7.01; 95 % CI = 3.14-15.64) and such association was synergistically significant. Salt tea consumption showed an interaction with genotypes of XPA and XPC. However, an interaction with FHC was significant in the case of XPA genotype only. XPA and XPC genotypes are associated with an increased risk of ESCC, and such association was reasonably modulated by different exposures.

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

Studies 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.

Leu432Val Polymorphism of CYP1B1 is Not Associated with Squamous Cell Carcinoma of Esophagus--a Case-Control Study from Kashmir, India.

BACKGROUND: Individual susceptibility to cancer has been attributed to polymorphisms in xenobiotic metabolizing genes. To evaluate the association of the Leu432Val polymorphism of cytochrome P4501B1 (CYP1B1) with esophageal squamous cell carcinoma (ESCC), we conducted a case control study in Kashmir, India, an area with a relatively high incidence of ESCC. MATERIALS AND METHODS: We recruited 404 histopathologically confirmed ESCC cases, and an equal number of controls, individually matched for sex, age and district of residence to respective cases. Information was obtained on various dietary, lifestyle and environmental factors in face to face interviews, using a structured questionnaire, from each subject. Genotypes were analysed by polymerase chain reaction, restriction fragment length polymorphism and sequencing of randomly selected samples. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Among the three possible variants, we did not find any Leu432Leu genotype of CYP1B1 in the study population and the genotypic distribution of Val432Val and Leu432Val carriers was nearly equal in both cases (89.6% and 10.4%) and controls (88.9% and 11.1%) respectively. We did not find any risk associated with this polymorphism in the current study (OR=0.64; 95% CI: 0.55-1.64). CONCLUSIONS: The study indicates that (Leu432Val) polymorphism of CYP1B1, is not associated with ESCC risk. However, replicative studies with larger sample size are needed to substantiate the findings.

Impediments in foreign collaboration and conducting a high throughput molecular epidemiology research in India, an assessment from a feasibility study.

BACKGROUND: Esophageal cancer is one of the world's top ten cancers. Its incidence, especially in the form of squamous cell carcinoma, is very high in some Asian regions including Kashmir. Jammu Kashmir and Ladakh are three provinces of Jammu and Kashmir, the northern most state of India. The three regions represent ethnically diverse socio-cultural populations with different incidences of esophageal squamous cell carcinoma (ESCC), a suitable setting for epidemiological studies. Hence, comparing the lifestyle, dietary habits and gene pools between the three regions will help in elucidation of ESCC etiology further. Therefore, to assess the possibility of conducting a larger case control study, we carried out a feasibility study to identify the collaborators as well as to explore patient referral systems and available research facilities in the state. FINDINGS: We found conducting good cancer molecular epidemiology studies is difficult due to lack of proper research facilities and favourable administrative guidelines. The appropriate storage, transportation and analyses facilities of biological specimens for genome-wide association study and assessment of nutrition and exposure markers are unavailable or not sufficiently developed. Guidelines that can encourage scientific collaborations within the country seem unavailable. However, the administrative guidelines available under which the export of biological specimens out of India for analysis seems impossible. Consequently, Indian researchers are unable to collaborate with foreign scientists and render state of art research facilities inaccessible to them. Scientists in other parts of India may also confront with most of these impediments. CONCLUSION: The study found that for conducting conclusive molecular epidemiological studies in India, referral system in hospitals is not systematic, scientific research facilities are inadequate as well as the guidelines for foreign collaboration  are not favourable.