Demographic profile of Cervical Cancer development: a hospital based study

Introduction: The present study is an attempt to detect Human papilloma virus infection along with its genotype in cancer cervix and its relation with demographic profile. Methods: Cervical cancer cases were enrolled in between Jan’ 2010 to Dec’ 2012. One sample was collected from non cancerous area of cervix for DNA extraction and two samples were collected from cancerous area of cervix from same patient, one for DNA extraction and other one for histopathological examination to confirm our clinical diagnosis. Extracted DNA was then checked for presence of HPV DNA by PCR amplification method using MY09/11 primer. HPV genotyping was done by using specific primer for HPV16 & HPV18. The cases were compared with their corresponding socio demographic profile. Results: The study showed 88.88% cases found to be HPV positive in cancerous area compared to 7.4% number in non cancerous area. Out of which 95.83% cases to be HPV 16 and only 4.16% were to be HPV 18 in cervical cancer cases. There were other significant risk factor association of cervical cancer with early marriage in 70.36% and high parity 87% of cases. Conclusion: The human papilloma virus type 16 & 18 are the major contributing factor along with other risk factors like early marriage, illiteracy and high parity for cervical cancer in our region

Epidemiology of cervical cancer development- a hospital based study

Introduction: The present study is an attempt to detect Human papilloma virus infection and immunomodulation status in the development of carcinoma cervix. Methods: Cervical cancer cases were enrolled in between Jan’ 2010 to Dec’ 2012. Cervical tissue biopsies from the both the cancerous region as well as the non cancerous control area of the cervix, and whole blood (3ml) were collected from all the study subjects. The tissue samples were collected either in PBS or RNA later solution in vials and stored in -80°C or liquid nitrogen till further use. Whole blood (2ml) was also collected from age matched voluntary female community controls (n=50), the plasma was separated, and stored at -20°C for cytokine analysis. Extracted DNA was then checked for presence of HPV DNA by PCR amplification method using MY09/11 primer. Th1 (IL-12) and Th2 (IL-10) were analysed both at protein as well as cervical tissue level. Results: The study showed 83.33% cases found to be HPV positive in cancerous area as well as in non cancerous area. There were other significant risk factor association of cervical cancer with early marriage in 70.36% and high parity 87% of cases. There is alteration of Th1 and Th2 ratio indicating immunomodulation plays an important role in the development of cervical cancer. Conclusion: The human papilloma virus infections are the major contributing factor as well as immunomodulation plays a major role in the development of cervical cancer in our region

Role of CYP2E1 gene polymorphisms association with hepatitis risk in Northeast India

AIM: To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India

High viral load and deregulation of the progesterone receptor signaling pathway: association with Hepatitis E-related poor pregnancy outcome

Background & Aims: Hepatitis E virus (HEV) infection is associated with high maternal and fetal mortalities. A prospective study was undertaken to evaluate the role of viral and host factors in HEV related pregnancy outcomes. Methods: The study included HEV infected pregnancy cases; acute viral hepatitis (AVH), n = 100 and fulminant hepatic failure (FHF), n = 43, and healthy pregnancy cases, n = 50. HEV genotypes and viremia were studied by nucleotide sequencing and real time PCR, respectively. Progesterone receptor (PR) gene mutations (PROGINS) were studied by PCR, PR expression at the mRNA and protein levels in the placenta were studied by semi-quantitative RT-PCR and immunohistochemistry, respectively. Progesterone induced blocking factor (PIBF) expression was studied by RT-PCR in blood. Serum interleukin-10 (IL-10) and interleukin-12 (IL-12) levels were assayed by ELISA. Results: HEV viral load was significantly higher in FHF than AVH (p <0.001) and in cases with fetal mortality in AVH (p = 0.001) and FHF (p = 0.018). PROGINS were predominant in FHF compared to AVH (p = 0.26) and showed reduced mRNA and protein expression. The risk of fetal mortality in AVH was two times higher (OR, 2.190; CI, 0.303-15.85) and maternal and fetal mortalities in FHF were 4-fold (OR, 4.0; CI, 0.363-44.113) increased in PROGINS carriers. PR and PIBF expression was lower in AVH and even lower in FHF compared to healthy controls. The higher IL-12/IL-10 ratio observed in FHF compared to other groups correlated with fetal mortality in AVH and FHF (p < 0.001). Conclusions: In conclusion, reduced expression of PR and PIBF, a higher IL-12/IL-10 ratio, and a high viral load results in poor pregnancy outcome in Hepatitis E

Role of polymorphic N-acetyl transferase2 (NAT2) and cytochrome P4502E1 (CYP2E1) gene in ATT induced hepatitis

Background and Aim: Antituberculosis drugs isoniazid and rifampicin in combination are known to develop drug induced hepatotoxicity (DIH). A higher risk of DIH during antituberculosis treatment (ATT) has been reported in Indian subcontinent compared to the western counterparts. The role of genetic factors in higher incidence of ATT hepatotoxicity in Indian population is still unclear. The present study was aimed at investigating the role of N-acetyltransferase2 (NAT2) and Cytochrome P4502E1 (CYP2E1) gene polymorphism in ATT hepatotoxicity. Design: The study population included 218 pulmonary tuberculosis patients who were started on ATT and followed up for the occurrence of ATT induced hepatitis. Genetic polymorphism of NAT2 and CYP2E1 gene was studied by PCR-RFLP. Results: Occurrence of DIH was 18.80% (41/218). There was a higher prevalence of NAT2 slow acetylator genotypes in DIH (70.73%) compared to non-DIH (44.63%), P &lt; 0.05. The frequency of NAT2<SUP>&#8727;</SUP>5/<SUP>&#8727;</SUP>7 and NAT2<SUP>&#8727;</SUP>6/<SUP>&#8727;</SUP>7 genotypes was significantly higher in DIH than non-DIH (19.51% vs. 6.78% and 19.51% vs. 5.08%). No association of CYP2E1 RsaI polymorphism could be demonstrated with DIH. However, DraI C/D genotype of CYP2E1 gene was mostly prevalent in DIH (85.37%) compared to non-DIH (64.41%), P &lt; 0.05. Slow acetylator status and CYP2E1 C/D or C/C genotype together showed higher frequency in DIH (65.85%) compared to non-DIH (28.81%), P &lt; 0.0001. Conclusion: The study demonstrates for the first time a possible association between DraI polymorphism of CYP2E1 gene and the risk of ATT hepatotoxicity. Genotyping of NAT2 and CYP2E1 gene could possibly identifying the high risk group for developing ATT induced hepatitis prior to medication

Exploring the p53 connection of cervical cancer pathogenesis involving north-east Indian patients.

BackgroundAs per WHO, Cervical cancer (CaCx) is a global issue, being the fourth common cancer in women with incidence rate of 13.1 per 1 lakh women globally and accounting for 311000 deaths in the year 2018 itself globally. The molecular pathogenesis in Human papillomavirus (HPV) infected cases is inconclusive. The detection of molecular factors leading to progression of CaCx can be important in the diagnosis and management of the disease. p53 a known tumor suppressor gene having a regulative role in cell cycle has been highlighted as key factor in the prevention of cancer but its significance in CaCx cases has been variably documented. The present study therefore targeted to evaluate the significance of p53 profile in CaCx cases in ethnically distinct northeast Indian population.MethodsBlood and Tissue samples (N = 85) of cervical cancer patients were collected and screening for HPV was performed using PCR. Thereafter the differential mRNA expression(qPCR), Immunohistochemistry, Mutation (PCR direct sequencing method) of p53 was studied. Further p53 epigenetic profiling was done by Methylation specific PCR (MS-PCR) and western blotting by using p53 acetylation specific antibodies.ResultsOur findings revealed that the downregulation of p53 was associated with the progression of disease and the variation in downregulation based on p53 polymorphism was observed. Further hypermethylation and deacetylation of p53 was also found to be associated with the pathogenesis of CaCx. The downregulated expression and hypermethylation of p53 in lower grade of CaCx, together established its association with the progression of CaCx from lower to severe grade.ConclusionTherefore, in CaCx patients of northeast Indian population, malfunctioning of p53 is found to have significant role in cervical cancer progression