Recent studies have reported that ACE may be involved in the development of tumors [21- 23]. ACE was a key enzyme in the renin-angiotensin system, which converted angiotensin I to angiotensin II and inactivates bradykinin. The mechanism of action may be due to the fact that angiotensin II can stimulate the synthesis of DNA and protein in vascular smooth muscle cells, and promote the synthesis and secretion of vascular endothelial growth factor . On the other hand, it may be because bradykinin can increase the permeability of the cell membrane to electrolytes and peptides. ACE can inactivate bradykinin  , but low expression of ACE in tumor tissues can promote invasive growth of malignant tumors. There are more and more published studies investigating the association between this polymorphism and lung cancer risk; however, there are inconsistencies and conflicts in the results. To further assess the association between ACE I/D polymorphism and lung cancer risk, we used a meta-analysis to analyze 12 case-control studies, including 2181 cases and 2126 controls.
The results of this meta-analysis showed no significant association was found in the three genetic models of comparison. Although previous studies have revealed that ACE may produce a certain effect in the etiology of lung cancer, our results suggest that these effects may not be caused by ACE gene mutations. The exact pathogenesis of AEC in the etiology of lung cancer remains unclear. Our results may suggest that ACE I/D polymorphism did not affect cancer risk. Moreover, considering that this polymorphism may affect serum ACE levels, and ACE levels may affect the risk of lung cancer, the risk of lung cancer is not directly caused by ACE gene mutation. Therefore, future research is necessary to determine the association between ACE polymorphism, ACE levels and cancer risk.
Previously, a meta-analysis was applied for eight published studies [7, 9, 10, 12, 14, 16-18] by Cheng et al , it included 1612 cases and 1442 controls, the results shown that the ACE gene I/D polymorphism was not associated with lung cancer. Wang et al  also conducted a meta-analysis of six published studies with 807 cases and 816 controls [7, 9, 12, 14, 17], the results also showed ACE I/D polymorphism may not be associated with lung cancer risk. In our study, a total of 12 studies were enrolled, including 2181 cases and 2126 controls. So the statistical power of the current analysis was better than the previous two meta-analyses. Compared with other studies, this study is more comprehensive about the relationship between ACE I/D polymorphism and lung cancer risk. Despite the differences between the studies included in the analysis, the results of our study suggest that the ACE I/D polymorphism may not lead to cancer risk, which is consistent with Cheng’s study and Wang ’s study.
However, there are certain limitations in our research. First, databases that include only published research in both Chinese and English are selected for analysis, and other language or unpublished potential research may be missed. Second, due to the lack of raw data, we were unable to assess potential interactions of gene-genes and genes-environments. Third, the meta-analysis includes data from Europeans and Asians, so the results of this item apply only to these two ethnic groups. Fourth, among the three models, heterogeneity may greatly influence the conclusion of the meta-analysis.