Cytokine gene polymorphisms and their association with cervical cancer: a north Indian study

Introduction: The production of cytokines, growth factors and adhesion molecules promotes tumor progression and involves inflammation, angiogenesis and thrombosis, thus providing optimal conditions for cancer development

Materials and methods: The present study was undertaken to evaluate association of cytokine gene polymorphisms with cervical cancer in a north Indian population. Genotyping of single nucleotide polymorphisms [SNPs] viz. IL-6-597G/A [rs1800797], IL-1[beta]-511C/T [rs16944] and TNF-[alpha]-308G/A [rs1800629] was carried out in 100 each of cases and healthy age matched controls by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP]. Genotype and allele frequencies were calculated by SPSS [ver.16] and gene-gene interaction was analyzed using SHEsis [ver. Online]

Results: Epidemiological studies showed that women >40 years have higher risk of cervical cancer due to early pregnancies. IL-6 and TNF-[alpha] promoter polymorphisms showed significant association [P < 0.001] while the SNP combinations G A T[Asterisk] and G G T[Asterisk] of IL-6-597A/G, TNF-[alpha]-308G/ A and IL-1[beta]-511C/T polymorphisms showed increased risk up to 9.0 and 3.30 times respectively

Conclusion:Therefore, the promoter polymorphisms in cytokine genes can be used as biomarkers to predict cervical cancer susceptibility in a north Indian population. However, such studies need to be carried out in different ethnic populations in order to discover the specific risk alleles, genotypes and combinations for disease prediction

Cyclooxygenase 1 [COX1] expression in type 2 diabetes mellitus: a preliminary study from north India

Background and purpose: The 6th edition of International Diabetes Federation, 2014 shows an estimate of 387 million people with Type 2 diabetes mellitus [T2DM] worldwide, expected to rise to 592 million by 2035. T2DM is a metabolic disorder, one of the reasons being oxidative stress due to impairment in antioxidant enzymes. It leads to several complications such as micro and macrovascular diseases. Cyclooxygenase1 [COX1] enzyme is the rate limiting factor for the arachidonic pathway leading to vascular wall contraction with angiotensin II occurring in heart diseases resulting from T2DM. COX1 determines 6-Keto Prostaglandin F1alpha [6-k-PGF1alpha] level, plays a major role in vasodilation and restricts macrophage platelet aggregation. The aim of the present study was to compare the COX1 expression and level of reactive oxygen species [ROS] in T2DM patients and controls at different time periods in human macrophages in order to find a biomarker or drug target

Subjects and methods: The study subjects consisted of 100 individuals, 50 each from T2DM patients and healthy sex/age matched controls. Cell proliferation by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assay and ROS measurement by 2',7'-dichlorofluorescein diacetate [DCFDA] staining were performed at different time periods [24, 48, 72 h]. COX1 mRNA expression was checked by relative quantification method after real-time polymerase chain reaction [RT-PCR]

Results: The MTT assay showed that cell viability was significantly higher at 48 h [P < 0.05]. ROS production was found to be lowest at 24 h by DCFDA staining. ROS levels were raised in T2DM patients as compared to controls. The quantitative RT-PCR analysis showed that the COX1 expression was higher in T2DM patients as compared to healthy controls although not significant [P > 0.05]

Conclusion: Although COX1 is known to be a "housekeeping" gene, our study showed that its expression can be correlated with the disease condition and be used as a marker. However, further studies are required in more number of samples from other ethnic populations to confirm the findings