angiotensinogen and Neoplasms

We assessed the relationship between AGT gene M235T polymorphism and the susceptibility to cancer by performing an updated meta-analysis. This study retrospectively searched related articles in the electronic databases. Afterwards, we determined combined odds ratios (ORs) and related 95% confidence intervals (CIs) by the fixed- or random-effects model. The present meta-analysis enrolled altogether 9 articles. On the whole, the relationship between AGT M235T polymorphism and the cancer risk was not significant among the entire population (TT vs. MM: OR = 1.28, 95%CI = 0.80 - 2.04; TM vs. MM: OR = 0.90, 95%CI = 0.53 - 1.52; recessive model: OR = 1.13, 95%CI = 0.83 - 1.52; dominant model: OR = 0.93, 95%CI = 0.55 - 1.57). Subgroup analysis by ethnicity, cancer type, and study quality for the relationship between the AGT M235T polymorphism and cancer risk showed no significant association. According to findings in the present meta-analysis, AGT M235T polymorphism may not be related to cancer susceptibility.

Topics: Angiotensinogen; Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Genetic; Retrospective Studies

The angiotensinogen (AGT) gene has been considered to be implicated in the development of cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of AGT M235T variant with cancer risk.. Published literature from PubMed and Embase were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using a fixed- or random-effects model.. A total of seven articles including eight studies (3639 cancer cases and 6684 controls) for AGT M235T variant were included. The present meta-analysis showed that AGT M235T variant was marginally associated with cancer risk under dominant model (OR=1.12, 95% CI=1.02-1.24). However, the positive association was not stable after sensitivity analysis. Further subgroup analysis by cancer type did not suggest any association of AGT M235T variant with various cancers (all p>0.05).. The present meta-analysis demonstrated that AGT M235T variant was not associated with risk of all cancer or various cancers. Further well-designed studies with large sample size should be conducted to confirm or refute the non-significant association.

Topics: Angiotensinogen; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Single Nucleotide; Publication Bias

Angiotensinogen (AGT) is a key component of renin-angiotensin-aldosterone system (RAAS), which plays central role in blood pressure homeostasis. Association of AGT polymorphisms have been investigated in different ethnic populations in variety of cardiovascular and non-cardiovascular conditions. In this study, 354 non-synonymous SNPs (nsSNPs) of AGT were evaluated to predict damaging and structurally important variants. Majority of the deleterious nsSNPs occurred in the evolutionary conserved regions. Several of these nsSNPs were found to affect post-translational modifications like methylation, glycosylation, phosphorylation, ubiquitination etc. Structural evaluations predicted 19 variants as destabilizing and some of them were also predicted to destabilize the renin-AGT interaction. Therefore, the present computational investigation predicted pathogenic and functionally important variants of human AGT gene. The study has also shown that AGT deregulation is associated with survival outcome in patients with gastric and breast cancer, using microarray gene expression profile. Furthermore, the computationally screened nsSNPs can be analyzed in population based genotyping studies and may help futuristic drug development in the area of AGT pharmacogenomics.

Topics: Amino Acid Sequence; Angiotensinogen; Humans; Neoplasms; Polymorphism, Single Nucleotide; Protein Processing, Post-Translational; Structure-Activity Relationship; Survival Rate; Thermodynamics