Upregulation of anaphase promoting complex (APC) 7 as a prognostic marker for esophageal squamous cell carcinoma: A hospital based study.

Esophageal cancer is the sixth leading cause of cancer death, and esophageal squamous cell carcinoma (ESCC) is the most prevalent type worldwide, with a poor prognosis due to late diagnosis. The search for new molecular prognostic biomarkers revealed that dysregulation of anaphase promoting complex/cyclosome (APC/C) activation due to altered expression of APC molecules might lead to perturbed mitotic progression leading to malignancy. We analyzed the expression of the four different subunits of the APC/C complex-APC3, APC4, APC5 and APC7-by Real Time Polymerase Chain Reaction (RT-PCR). The findings were then correlated with clinicopathological parameters and different lifestyle factors. Significant upregulation of APC7 (tissue and blood: N = 50; 3.72 ± 1.21 and 4.45 ± 1.18, respectively) and APC3 (tissue and blood: N = 52 and 55 and 4.50 ± 1.41 and 4.58 ± 1.06, respectively) suggests their role in uncontrolled cell proliferation. In addition to their association with increasing age, their significant association with tumor size, node stage (only APC7 (p < 0.05)), and dysphagia grade supports a potential role in tumorigenic transformation in ESCC. Furthermore, several exclusive lifestyle-associated factors play a crucial supporting role in the development of ESCC in the Northeast Indian population. Various lifestyle factors, such as the duration of smoking, tobacco and betel nut consumption, and the duration of alcohol consumption, are significantly associated with the expression of APC. Analysis based on Pearson's correlation coefficient indicated a positive correlation among the gene expression levels ofAPC3 (both blood and tissue), APC5 (tissue) and APC3 (tissue), APC7 (tissue) and APC3 (tissue), and APC7 (tissue) and APC3 (blood). Additionally, a positive correlation was found between APC7 expression in blood and tissue samples. However, no significant correlation was found between APC 7 expression and APC4 and APC5 expression in either blood or tissue samples.

Altered expression of TGF-ß1 and TGF-ßR2 in tissue samples compared to blood is associated with food habits and survival in esophageal squamous cell carcinoma.

In the transforming growth factor ß (TGF-ß) signaling pathway, TGF-ß1 and TGF-ß receptor 2 (TGF-ßR2) are essential regulatory components which play an important role in different type of cancer. Expressions of TGF-ß1 and TGF-ßR2 were done by real-time qPCR in both biopsy and blood samples collected from esophageal squamous cell carcinoma (ESCC) patients (n = 76). The expression profiles were correlated with different lifestyle factors and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression analysis were performed to estimate survival and hazard outcomes of different parameters. TGF-ß1 showed upregulation in 91% tissue samples (2.84 ± 1.34*) and 55% blood samples (2.43 ± 1.24*) whereas expression of TGF-ßR2 showed downregulation in 89% tissue samples (0.27 ± 0.23*) and 75% blood samples (0.30 ± 0.26*). Among all the parameters, TGF-ß1 expression is significant with histopathology grade, consumption of betel nut and smoked food whereas TGF-ßR2 expression is significant only with dysphagia grade in both blood and tissue samples and while analyzing both male and female patients separately. Consuming alcohol and hot food, difference in tumor stage and metastasis were found to have statistically significant (P < 0.05) impact on survival and mortality of male patients while consuming hot food, tobacco, metastasis and TGF-ßR2 expression in tissue level were found to associate with survival and mortality of female patients. Expression of both TGF-ß1 and TGF-ßR2 in tissue samples may be prospective biomarkers for screening of ESCC among the Northeast population. Survival outcomes and hazard analysis supports the importance of some clinicopathological and lifestyle factors on ESCC development, whereas expression study depicts association of change in expression of the studied genes in ESCC patients. *Mean fold change.

Genetic Polymorphisms Along with Dietary and Environmental Factors Enhance the Susceptibility to Nasopharyngeal Carcinoma in Nagaland of Northeast India.

This study investigated the association of seven widely known DNA repair gene polymorphisms (hOGG1 Ser326Cys, XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPC Val499Ala, XPD Lys751Gln and ERCC1 Cys8092Ala) with dietary and environmental factors for Nasopharyngeal Carcinoma (NPC) susceptibility in Nagaland of Northeast India. The genotypes were determined in 128 NPC patients and 180 healthy controls by PCR-RFLP. XRCC1 Arg280His, XPC Val499Ala and ERCC1 Cys8092Ala were found to be associated with NPC risk. Tobacco smoking and burning of firewood for cooking were also found to be a risk factor for NPC. The haplotype analysis of five single-nucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPD Lys751Gln and ERCC1 Cys8092Ala identified haplotype TGAAC to be significantly associated with NPC. Multifactor dimensionality reduction (MDR) analysis suggested ERCC1 Cys8092Ala to be the best one-factor model that could predict NPC risk. From this study, we conclude that examining the synergistic interactions of various gene-environmental factors together is a better approach to understand NPC susceptibility, instead of their individual effects.

Determination of individual type 2 diabetes risk profile in the North East Indian population & its association with anthropometric parameters.

Background & objectives: Diabetes genomics research has illuminated single nucleotide polymorphism (SNP) in several genes including, fat mass and obesity associated (FTO) (rs9939609 and rs9926289), potassium voltage-gated channel subfamily J member 11 (rs5219), SLC30A 8 (rs13266634) and peroxisome proliferator-activated receptor gamma 2 (rs1805192). The present study was conducted to investigate the involvement of these polymorphisms in conferring susceptibility to type 2 diabetes (T2D) in the North East Indian population, and also to establish their association with anthropometric parameters. Methods: DNA was extracted from blood samples of 155 patients with T2D and 100 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. To confirm the association between the inheritance of SNP and T2D development, logistic regression analysis was performed. Results: For the rs9939609 variant (FTO), the dominant model AA/(AT+TT) revealed significant association with T2D [odds ratio (OR)=2.03, P=0.021], but was non-significant post correction for multiple testing (P=0.002). For the rs13266634 variant (SLC30A 8), there was considerable but non-significant difference in the distribution pattern of genotypic polymorphisms between the patients and the controls (P=0.004). Significant association was observed in case of the recessive model (CC+CT)/TT (OR=4.56 P=0.001), after adjusting for age, gender and body mass index. In addition, a significant association (P=0.001) of low-density lipoprotein (mg/dl) could be established with the FTO (rs9926289) polymorphism assuming dominant model. Interpretation & conclusions: The current study demonstrated a modest but significant effect of SLC30A8 (rs13266634) polymorphisms on T2D predisposition. Considering the burgeoning prevalence of T2D in the Indian population, the contribution of these genetic variants studied, to the ever-increasing number of T2D cases, appears to be relatively low. This study may serve as a foundation for performing future genome-wide association studies (GWAS) involving larger populations.