Candidate gene studies in gallbladder cancer: A systematic review and meta-analysis

Abstract

Gallbladder cancer (GBC) is the most frequent biliary tract malignancy. Wide variations in GBC incidence and familial and epidemiological data suggest involvement of a genetic component in its etiopathogenesis. A systematic review of genetic association studies in GBC was performed by applying a meta-analysis approach and systematically reviewing PubMed database using appropriate terms. Odds ratios (ORs) and 95% confidence intervals (CIs) were appropriately derived for each gene–disease association using fixed and random effect models. Meta-regression with population size and genotyping method was also performed. Study quality was assessed using a 10-point scoring system designed from published guidelines. Following a review of 44 published manuscripts and one unpublished report, 80 candidate gene variants and 173 polymorphisms were analysed among 1046 cases and 2310 controls. Majority of studies were of intermediate quality. Four polymorphisms with > 3 separate studies were included in the meta-analysis [OGG1 (rs1052133), TP53 (rs1042522), CYP1A1 (rs1048943) and GSTM1 Null polymorphism]. The meta-analysis demonstrated no significant associations of any of the above polymorphisms with GBC susceptibility. To conclude, existing candidate gene studies in GBC susceptibility have so far been insufficient to confirm any association. Future research should focus on a more comprehensive approach utilizing potential gene–gene, gene–environment interactions and high-risk haplotypes.

Modifiable Factors and Genetic Predisposition Associated with Gallbladder Cancer. A Concise Review

“…Such associations, however, have only been found in single populations and need to be confirmed in larger populations of different ethnicity. A systematic review and, where sufficient data available, meta-analysis of 80 candidate gene variants and 173 polymorphisms among 1046 cases and 2310 controls revealed that most studies were underpowered or, as observed for 8-oxoguanine DNA glycosylase (OGG1, rs1052133), TP53 (rs1042522), CYP1A1 (rs1048943) and glutathione S-transferase mu 1 (GSTM1) Null polymorphisms, could not confirm previous association results upon meta-analysis [50].…”

“…A substantial number of casecontrol association studies in patients from India and China are providing interesting leads as to candidate gene SNPs for GbCa susceptibility. Results from most of these studies have been comprehensively reviewed previously [50], thus we are not presenting a full list of candidate association studies in this review but rather an exemplary selection. Variants in genes for, among others, estrogen receptors [51], cholecystokinin type A receptor [52], adrenergic receptor [53] or the cholesterol hemitransporter ABCG8 [54,55] increase the risk for GbCa by about 2-3 fold (Table II).…”

Association of TNF-α-308(G/A) and -238(G/A) polymorphisms with non-traumatic osteonecrosis of the femoral head risks: a meta-analysis

“…Clark scores system, which contains ten items [34], was implemented to assess the qualities of the included studies by two investigators independently. Scores below 5 were regarded as low quality, while 5-7 scores indicate moderate quality and 8-10 scores represent high quality [34].…”

“…Scores below 5 were regarded as low quality, while 5-7 scores indicate moderate quality and 8-10 scores represent high quality [34].…”

Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations

“…More recently, the cancer research field has begun to understand the importance of rare deleterious germline variants in carcinogenesis and progression (28,29,37). GBC is not among the most heritable types of human cancer, although variability in its ethnic and geographical incidence rates has been partly associated with cancer predisposition (38)(39)(40). Recently, we reported a genome-wide association study recruiting cases of GBC, it outlined the contribution of common variants to GBC predisposition.…”