ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2014
A multigenic approach to evaluate genetic variants of PLCE1, LXRs, MMPs, TIMP, and CYP genes in gallbladder cancer predisposition.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Interactions of genetic variations in FAS, GJB2 and PTPRN2 are associated with noise-induced hearing loss: a case-control study in China.BMC medical genomics · 2024Article
- An integrative pan-cancer analysis of molecular characteristics and oncogenic role of mitochondrial creatine kinase 1A (CKMT1A) in human tumors.Scientific reports · 2022Article
- Comprehensive bioinformation analysis of the miRNA of PLCE1 knockdown in esophageal squamous cell carcinoma.Molecular and cellular biochemistry · 2018Article
- Single Nucleotide Polymorphisms inFrontiers in oncology · 2018Article
- Association ofOncotarget · 2017Article
- Association between PSCA gene polymorphisms and the risk of cancer: an updated meta-analysis and trial sequential analysis.Oncotarget · 2017Article
- PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy.Oncotarget · 2017Article
- Fine-Mapping of ABO Gene Identifies Two Novel SNPs Associated with Large Artery Atherosclerotic Stroke in a Chinese Han Population.Molecular neurobiology · 2017Article
- Article
- Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma.Oncotarget · 2016Article
- A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations.International journal of molecular sciences · 2015Article
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7 authors.
Funding
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Abstract
Gallbladder cancer (GBC) is a violent neoplasm associated with late diagnosis, unsatisfactory treatment, and poor prognosis. The disease shows complex interplay between multiple genetic variants. We analyzed 15 polymorphisms in nine genes involved in various pathways to find out combinations of genetic variants contributing to GBC risk. The genes included in the study were matrix metalloproteinases (MMP-2, MMP-7, and MMP-9), tissue inhibitor of metalloproteinases (TIMP-2), cytochrome P450 (CYP)1A1, CYP1B1, phospholipase C epsilon 1 (PLCE1), liver X receptor (LXR)-alpha, and LXR-beta. Genotypes were determined by PCR-RFLP and TaqMan probes. Statistical analysis was done by SPSS version 16. Multilocus analysis was performed by Classification and Regression Tree (CART) analysis and multifactor dimensionality reduction (MDR) to gene-gene interactions in modifying GBC risk. In silico analysis was done using various bioinformatics tools (F-SNP, FAST-SNP). Single locus analysis showed association of MMP-2 (-735 C > T, -1306 C > T), MMP-7 - 181 A > G, MMP-9 (P574R, R668Q), TIMP-2 - 418 G > C, CYP1A1-MspI, CYP1A1-Ile462Val, PLCE1 (rs2274223 A > G, rs7922612 T > C) and LXR-beta T > C (rs3546355 G > A, rs2695121 T > C) polymorphisms with GBC risk (p < 0.05) whereas CYP1B1 and LXR-α variants were not associated with GBC risk. Multidimensional reduction analysis revealed LXR-β (rs3546355 G > A, rs2695121 T > C), MMP-2 (-1306 C > T), MMP-9 (R668Q), and PLCE1 rs2274223 A > G to be key players in GBC causation (p < 0.001, CVC = 7/10). The results were further supported by independent CART analysis (p < 0.001). In silico analysis of associated variants suggested change in splicing or transcriptional regulation. Interactome and STRING analysis showed network of associated genes. The study found PLCE1 and LXR-β network interactions as important contributory factors for genetic predisposition in gallbladder cancer.
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