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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. [ABSTRACT FROM AUTHOR]

Unlike many other cancers, the relationship ofCYP1A2*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) ofCYP1A2*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 ofCYP1A2*1F (OR = 14.51; 95% CI: 5.33–39.47). The study indicates thatCYP1A2*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. [ABSTRACT FROM PUBLISHER]

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) 2C19andCYP2D6genotypes 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 ofCYP2C19(OR = 3.3) orCYP2D6(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 ofCYP2C19(OR = 4.4) orCYP2D6(OR = 4.7). Risk was appreciably increased in subjects who had family history of any cancer and also harbored a variant genotype of eitherCYP2C19(OR = 15.5) orCYP2D6(OR = 9.7). Subjects harboring a variant genotype ofCYP2D6showed an added risk when they used biomass as fuel (OR = 4.6). In conclusion, variant genotypes ofCYP2C19andCYP2D6are associated with an increased risk of ESCC. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Aim: The aim of our study was to investigate whether the tandem repeat polymorphism in D18S452 microsatellite marker at locus 18p11.2 is a risk factor of bipolar affective disorder (BPAD) in Kashmiri population. Materials and Methods: The repeat polymorphism in D18S452 was evaluated by polymerase chain reaction (PCR) analysis of in 74 diagnosed BPAD patients and 74 controls subjects. Results: Tandem repeat (300 bp") allele frequency was found to be 1.35% in controls and 8.108% in cases. The tandem repeat (250 bp") allele frequency was found to be in 91.89% in cases and 98.65% in controls. The 252 bp/252 bp genotype was found to be present in 89.18% of cases and 98.64% of controls, the 300 bp/300 bp genotype in 5.40% of cases and 1.35% of controls and the 252 bp/300 bp variant in 5.40% of cases and none among the controls. Although the proportion of patients homozygous for tandem repeat (300 bp/300 bp) was higher in cases than in controls, the difference was not statistically significant when 252 bp/252 bp genotype was taken as reference (odds ratio [OR]=4.4242; 95% confidence interval [CI] 0.4822-40.5924); P=0.1529). However, when the frequency of heterozygous genotype (252 bp/300 bp) was compared with 252 bp/252 bp statistical significance was observed (OR=8.0603; 95% CI 1.1112-58.4646; P=0.0383). Conclusion: This is the first study reporting a significant association between D18S452 maker with tandem repeat polymorphism in heterozygous condition (252 bp/300 bp) and the development of BPAD in Kashmiri population. [ABSTRACT FROM AUTHOR]

Nuclear factor kappa B signaling pathway and cyclooxygenase-2 are considered molecular prototypes for targeting various diseases including inflammation. Aconitum chasmanthum has been used for decades to cure different ailments as its anti-inflammatory and anti-analgesic effects are well documented, but the mechanism remains unknown. Thus, in current study, we attempted to assess the anti-inflammatory characteristics of Aconitum chasmanthum which can be regarded as an appealing therapeutic candidate. In present study, High-Resolution Liquid Chromatography and Mass Spectrophotometry (HRLCMS-QTOF-MS) method were used to determine the phytoconstituents in the methanolic extract of wild rhizome of Aconitum chasmanthum. The in vitro studies were done on HCT-116 cell line and an MTT assay was used to assess the cell viability (IC 50 value). In the present study, mRNA expression of pro-inflammatory genes (nuclear factor kappa B 1 , nuclear factor kappa B 3 (RelA), and cyclooxygenase-2) was determined via quantitative polymerase chain reaction and western blot. Molecular docking analysis was performed by Auto Dock Vina to find potential compounds having anti-cyclooxygenase-2 activity. The current investigations found that methanolic extract strongly downregulates the gene expression of pro-inflammatory genes at a concentration of 200 μg/mL. While as western blot results showed a significant decrease in cyclooxygenase-2 protein level at 200 μg/mL concentration for 48 hrs. ADMET analysis revealed the physiochemical properties of bioactives and a drug. Molecular docking revealed staurosporine was the most effective compound against COX-2 with the highest binding affinity of − 9.7 kcal/mol. Thus the findings of current study reveal that Aconitum chasmanthum possesses substantial anti-inflammatory/anti-analgesic properties and therefore can be used to develop novel anti-inflammatory and anti-analgesic drugs in future. [Display omitted] • A. chasmanthum extract strongly down regulated the gene expression of NF-κB1, RelA and COX-2 at 200 µg/mL concentration in the HCT-116 cell line. • In-silico study determined strong binding affinities of certain phytocompounds against COX-2 protein. [ABSTRACT FROM AUTHOR]