The Number of Lymph Node Metastases in Gastric Cancer Correlates with the Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism

Abstract

Purpose: In the present study, we aimed to substantiate the putative significance of angiotensin I^converting enzyme (ACE) on gastric cancer biology by investigating the influence of its gene polymorphism on gastric cancer progression. Experimental Design: Genomic DNA was purified from peripheral blood mononuclear cells or tissue specimens. Amplified ACE gene fragments were separated on agarose gels. D or I alleles were identified by the presence of 190-or 490-bp fragments, respectively. Local expression of ACE was investigated by immunohistochemistry. Results: Twenty-four of 113 (21%) gastric cancer patients had the II, 57 (51%) the ID, and 32 (28%) the DD genotype. The distribution of the ACE genotypes did not differ significantly from the control group of 189 patients without gastric cancer. However, the ACE genotypes correlated with the number of lymph node metastases and the Unio Internationale Contra Cancrum (UICC) tumor stage. Patients with the II genotype had a highly significantly smaller number of lymph node metastases (P < 0.001) and a significantly lower UICC tumor stage (P = 0.01) than patients with the DD genotype. No correlation was found between tumor type, tumor location, local tumor growth, distant metastases, and the ACE genotype. The expression of ACE in gastric cancer was investigated by immunohistochemistry in 100 of 113 patients. ACE was expressed by endothelial cells in all (100%) specimens and by tumor cells in 56 (56%) specimens. Conclusions: Our study shows that ACE is expressed locally in gastric cancer and that the gene polymorphism influences metastatic behavior.

Lack of any Association between Insertion/Deletion (I/D) Polymorphisms in the Angiotensin-converting Enzyme Gene and Digestive System Cancer Risk: a Meta-analysis

“…ACE may not affect the incidence of digestive system cancer, however, it may affect the progression of digestive system cancer. Rocken et al have found that the gene polymorphism influence the metastatic behavior of gastric cancer (Rocken et al, 2005).Thus, future studies are warranted to identify the associations between ACE polymorphism and the risk of progression and metastasis of digestive system cancer.…”

“…Genotype and allele distributions for each case-control study are shown in Table 2. There were 7 studies of Asians (Goto et al, 2005;Sugimoto et al, 2006;Hou et al, 2010;Hibi et al, 2011;Liu et al, 2011;Ji et al, 2012;Yuan et al, 2013), 8 of Europeans (Ebert et al, 2005;Rocken et al, 2005;Nikiteas et al, 2007;Rocken et al, 2007;van der Knaap et al, 2008;Toma et al, 2009;Kupcinskas et al, 2011;Lukic et al, 2011). In this meta-analysis, the most studied cancers were gastric cancer and colorectal cancer, the genotype methods are a classic PCR assays.…”

“…Recent years, many studies investigated the role of this polymorphism in the etiology of digestive system cancer (Rocken et al, 2005;Kupcinskas et al, 2011;Yuan et al, 2013). However, the observed associations of these studies…”

Insertion/deletion (I/D) in the Angiotensin-converting Enzyme Gene and Breast Cancer Risk: Lack of Association in a Meta-analysis

“…Angiotensin II (Ang II), the main biologically active peptide of the RAS, is converted from angiotensin I (Ang I) via angiotensin I-converting enzyme (ACE).ACE is differentially expressed in several carcinomas and may affect tumor cell proliferation,migration and angiogenesis (Rocken et al, 2005). The human ACE gene contains many polymorphisms,which is located on chromosome RESEARCH ARTICLE Insertion/deletion (I/D) in the Angiotensin-converting Enzyme Gene and Breast Cancer Risk: Lack of Association in a Metaanalysis Xin-Hong Pei 1,3 , Hui-Xiang Li 2,3 * 17q23, and the 287-bp Alu insertion/deletion (I/D, rs4646994) polymorphism in intron 16 is widely studied (Haiman et al, 2003), and ACE I/D polymorphism has been related to ACE levels (Villard et al, 1996).…”

Angiotensin inhibition and malignancies: a review

“…Röcken et al 76 reported that ACE is expressed locally in gastric cancer and that the ACE gene polymorphism influences metastatic behaviour. Twenty-four of 113 (21%) gastric cancer patients had the II, 57 (51%) the ID, and 32 (28%) the DD genotype.…”