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Introduction: miR-27a, miR-181a, and miR-570 genetic variants have been found to play an important role in many cancers, but their contribution in gallbladder carcinoma (GBC) has not been explored. Therefore, we investigated the role of these micro RNA (miRNA) genetic variants in terms of GBC susceptibility, therapeutic response, toxicities associated with chemo-radiotherapy and survival outcome. Methods: This study included 606 GBC patients and 200 healthy controls. From among the larger study cohort, 219 patients receiving adjuvant or palliative chemo-radiotherapy as per disease status were followed up for toxicity profile. Treatment response was recorded in 159 patients who received palliative chemo-radiotherapy. Genotypes were determined using allelic discrimination assay. Statistical analysis was carried out with SPSS version 16. Generalized multifactor dimensionality reduction (GMDR) analysis was performed for gene-gene interactions. Survival analysis was performed using Kaplan-Meier and Cox regression tests. Results: In univariate logistic regression analysis, no association with any of the studied polymorphisms was found in overall GBC susceptibility. Furthermore, univariate and multivariate analyses revealed no significant association with response to chemo-radiotherapy. In GMDR analysis, miR-27a, miR-570, and miR-181a combination was found as the best gene-gene interaction model for susceptibility and treatment response. Furthermore, miR-27amiR-181a was associated with neutropenia toxicity in patients undergoing chemo-radiotherapy. However, miRNA variants had no influence over the survival outcomes of GBC patients (locally advanced, metastatic). Conclusion: In conclusion, the miRNA variants cumulatively influence GBC susceptibility and treatment outcomes. [ABSTRACT FROM AUTHOR]

Background and Aim: Defective apoptosis is a hallmark of cancer development and progression. Death receptors (DR4, FAS) and their ligands (TRAIL, FASL) are thought to mediate the major extrinsic apoptotic pathway in the cell. SNPs in these genes may lead to defective apoptosis. Hence, the present study aimed to investigate the association of functional SNPs of DR4 (rs20575, rs20576 and rs6557634), FAS (rs2234767) and FASL (rs763110) with gallbladder cancer (GBC) risk. Methods: This case-control study included 400 GBC and 246 healthy controls (HC). Genotyping was carried out by Taqman genotyping assays. Statistical analysis was performed by using SPSS ver16. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) to systematically summarize the possible association of SNP with cancer risk. Functional prediction of these variants was carried out using Bioinformatics tools (FAST-SNP, F-SNP). False discovery rate (FDR test) was used in multiple comparisons. Results: The DR4 Crs20575Ars20576Ars6557634, Grs20575Ars20576Grs6557634 and Grs20575Crs20576Grs6557634 haplotypes conferred two-fold increased risk for GBC. Among these, the DR4 Crs20575Ars20576Ars6557634 haplotype emerged as main factor influencing GBC susceptibility as the risk was not modulated by gender or gallstone stratification. Our meta-analysis results showed significant association of DR4 rs6557634 with overall cancer risk, GI cancers as well as in Caucasians. We didn't find any association of FAS and FASL SNPs with GBC susceptibility. Conclusions: The DR4 haplotype Crs20575Ars20576Ars6557634 represents an important factor accounting the patients susceptibility to GBC probably due to decreased apoptosis. However, additional well-designed studies with larger sample size focusing on different ethnicities are required to further validate the results. [ABSTRACT FROM AUTHOR]

Background Matrix metalloproteinase belong to family of pericellular collagenases which degrade extracellular matrix ( ECM), and is involved in the modulation and susceptibility of various cancers. Methodology The present study included 410 gallbladder ( GBC) cases and 230 healthy controls from North India. Study examined the associations of polymorphisms of MMP -2c.735C>T (rs2285053), MMP -2c.1306 C>T (rs243865), MMP 7c.181A>G (rs11568818), MMP -9p.R279Q (rs17556) MMP -9p.P574R (rs2250889), MMP -9 p.R668Q (rs17577) and TIMP 2c.418 G>C (rs8179090) to GBC susceptibility. Genotyping was carried out by PCR- RFLP. Statistical analysis was performed by using SPSS ver16. Results The MMP -2 c.735 [ CT+ TT] , MMP -2c.1306 [ CT+ TT] , MMP 7 c.181 [ AG+ GG] and MMP -9 p.668 [ RQ+ QQ] , TIMP 2c.418 [ GG+ GC] genotypes were significantly associated with increased risk of GBC ( P = 0.01; [ OR]1.87, P = 0.02; [ OR] 1.68, P = 0.02; [ OR]=1.61, P = 0.002; [ OR]=1.91, P = 0.01; [ OR]=1.78 and ( P = 0.03; [ OR]=1.68; P = 0.01; [ OR]=1.78 respectively). Haplotypes [C-735-T-1306] and [T-1306-C-735] of MMP -2 ( P = <0.005; [ OR] =1.78 P = <0.0001; [ OR] =2.09) and haplotype [Q279-P574-Q668]of the MMP -9 ( P = 0.04; [ OR] =2.75) were significantly associated with GBC risk. On stratification of GBC patients with/without gallstones, MMP -2 haplotypes were associated with higher GBC risk in patients accompanying gallstones whereas MMP -9 haplotypes showed risk in patients without stones. Combined effect of > 3 MMP / TIMP variant containing genotypes imparted increased risk of GBC ( P < 0.0001; [ OR] =3.36). Multivariate logistic regression results also supported association of MMP -2 (c.735C>T, c.1306 C>T) , MMP -9 p.R668Q and TIMP 2c.418G>C variants with GBC susceptibility. Conclusion This study suggests that genetic variants in MMP -2,7,9 and TIMP -2genes are associated with higher susceptibility of gallbladder cancer. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this diagnostic observational study was to assess the spread and biological behavior of gallbladder cancer using 64-slice computerized tomography (CT) scanner in this particular geographic belt (eastern Uttar Pradesh, western Bihar, and northern Madhya Pradesh provinces of North India). Indians are ethnically and culturally different from their Western counterparts among whom the incidence of this disease is comparatively low. Subjects and Methods: After systemic examination, all patients (87) were subjected to ultrasonographic examination. All cases were histopathologically proven. Confirmed cases were subjected to volumetric CT examination of abdomen and pelvis, plain, post contrast and delayed phase. Results: Majority of the cases were adenocarcinoma. There was female preponderance with majority belonging to fifth and sixth decades. Commonest presentation was diffuse, irregular, enhancing wall thickening in 49.4%. Majority had invasion of liver parenchyma (74.7%). Cholelithiasis was seen in 48.3% cases. Invasion of biliary radicals was high (13.8-18.4%). Eleven cases had invasion of portal vein and tumor thrombus, with hepatic artery invasion in one case. In two cases, both hepatic artery and portal vein invasion was seen. Portal and peripancreatic nodal metastasis was seen in 58.5%. Distant metastasis was reported. Conclusion: Few studies involving the Indian population have attempted to use multi-row detector CT to define the biological behavior of carcinoma gallbladder. The opinion whether the pathology is operable or non-operable can reasonably be given. This large-scale, single-center study gives insight about the epidemiology and biological behavior of carcinoma gallbladder. [ABSTRACT FROM AUTHOR]

Gall bladder cancer (GBC) is a relatively rare but highly fatal disease, particularly in North India. The angiotensin I-converting enzyme ( ACE) insertion/deletion (I/D) gene polymorphism influences serum angiotensin II action, which has been associated with various malignancies. This population-based case–control study was undertaken to examine the potential association of ACE I/D variation with GBC in a North Indian population. Genotypes and allelic frequencies of the ACE I/D polymorphism (rs4646994) were determined for 233 GBC patients and 260 cancer-free controls randomly selected from the population using polymerase chain reaction. Odds ratio (OR) and 95% confidence interval were calculated in multivariate logistic regression analysis for the association of ACE polymorphism with GBC. The ACE I/D polymorphism was found to be nonsignificantly associated with an overall increased risk of GBC (OR = 1.04 and 1.38 for I/D and D/D genotypes, respectively; ptrend = 0.375). The increased risk was predominant significantly in female cohort and nonsignificantly in GBC patients with gallstone status (OR = 1.63; p = 0.039 and OR = 1.37; p = 0.187, respectively). In summary, ACE I/D polymorphism may alter the susceptibility to GBC, especially in women. [ABSTRACT FROM AUTHOR]