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

  • Liu, Jin-Fei (Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Southern Medical University) ;
  • Xie, Hao-Jun (Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University) ;
  • Cheng, Tian-Ming (Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Southern Medical University)
  • Published : 2013.12.31


Objective: To investigate the association between the gene polymorphisms of angiotensin-converting enzyme (ACE) and digestive system cancer risk. Method: A search was performed in Pubmed, Medline, ISI Web of Science and Chinese Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical analysis was performed by using Revman5.2 and STATA 12.0. Results: A total of 15 case-control studies comprising 2,390 digestive system cancer patients and 9,706 controls were identified. No significant association was found between the I/D polymorphism and digestive cancer risk (OR=0.93, 95%CI = (0.75, 1.16), P=0.53 for DD+DI vs. II). In the subgroup analysis by ethnicity and cancer type, no significant associations were found for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated a lack of associations between this polymorphism and digestive system cancer risks. Conclusions: This meta-analysis suggested that the ACE D/I polymorphism might not contribute to the risk of digestive system cancer.


  1. Abali H, Gullu IH, Engin H, et al (2002). Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists. Med Hypotheses, 59, 344-8.
  2. Bauvois B (2004). Transmembrane proteases in cell growth and invasion: new contributors to angiogenesis? Oncogene, 23, 317-29.
  3. Ebert MP, Lendeckel U, Westphal S, et al (2005). The angiotensin I-converting enzyme gene insertion/deletion polymorphism is linked to early gastric cancer. Cancer Epidemiol Biomarkers Prev, 14, 2987-9.
  4. Goto Y, Ando T, Nishio K, et al (2005). The ACE gene polymorphism is associated with the incidence of gastric cancer among H. pylori seropositive subjects with atrophic gastritis. Asian Pac J Cancer Prev, 6, 464-7.
  5. Haiman CA, Henderson SO, Bretsky P, Kolonel LN, Henderson BE (2003). Genetic variation in angiotensin I-converting enzyme (ACE). and breast cancer risk: the multiethnic cohort. Cancer Res, 63, 6984-7.
  6. Hibi S, Goto Y, Ando T, et al (2011). No association between angiotensin I converting enzyme (ACE). I/D polymorphism and gastric cancer risk among Japanese. Nagoya J Med Sci, 73, 169-75.
  7. Hou AJ, Zhou L, Hu Y, et al (2010). The ACE gene polymorphism of angiotensin-converting enzyme in 30 cases of colon cancer patients(chinese). Chinese J Ethnomed Ethnoph, 99-100.
  8. Ji SW, Mao XD, Liu JM, et al (2012). The gene polymorphism of angiotensin-converting enzyme in patients with esophageal cancer. Acta Universitatis Medicinalis Anhui, 34, 35-8 (in Chinese).
  9. Kitsios G, Zintzaras E (2009). ACE (I/D). polymorphism and response to treatment in coronary artery disease: a comprehensive database and meta-analysis involving study quality evaluation. BMC Med Genet, 10, 50.
  10. Kupcinskas J, Wex T, Bornschein J, et al (2011). Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pyloriinduced premalignant gastric lesions and gastric cancer in Caucasians. BMC Med Genet, 12, 112.
  11. Lever AF, Hole DJ, Gillis CR, et al (1998). Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet, 352, 179-84.
  12. Liu SY, Sima X, Wang CH, Gao M (2011). The association between ACE polymorphism and risk of colorectal cancer in a Chinese population. Clin Biochem, 44, 1223-6.
  13. Lukic S, Nikolic A, Alempijevic T, et al (2011). Angiotensinconverting enzyme gene insertion/deletion polymorphism in patients with chronic pancreatitis and pancreatic cancer. Dig Surg, 28, 258-62.
  14. Meyer BR, Vashishtha A (1995). Angiotensin-convertingenzyme genotype and ischemic heart disease. N Engl J Med, 333, 458-459, 459-460.
  15. Nikiteas N, Tsigris C, Chatzitheofylaktou A, Yannopoulos A (2007). No association with risk for colorectal cancer of the insertion/deletion polymorphism which affects levels of angiotensin-converting enzyme. In Vivo, 21, 1065-8.
  16. Rigat B, Hubert C, Alhenc-Gelas F, et al (1990). An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest, 86, 1343-6.
  17. Rocken C, Lendeckel U, Dierkes J, et al (2005). The number of lymph node metastases in gastric cancer correlates with the angiotensin I-converting enzyme gene insertion/deletion polymorphism. Clin Cancer Res, 11, 2526-30.
  18. Rocken C, Neumann K, Carl-McGrath S, et al (2007). The gene polymorphism of the angiotensin I-converting enzyme correlates with tumor size and patient survival in colorectal cancer patients. Neoplasia, 9, 716-22.
  19. Srivastava K, Srivastava A, Mittal B (2010). Angiotensin I-converting enzyme insertion/deletion polymorphism and increased risk of gall bladder cancer in women. Dna Cell Biol, 29, 417-22.
  20. Su ZH, Wang RH, Yang SX, et al (2013). Study of ACE gene polymorphism and disease susceptibility in hui-chinese gastric cancer in Qinghai province(chinese). J Qinghai Med College, 34, 1-6.
  21. Sugimoto M, Furuta T, Shirai N, et al (2006). Influences of chymase and angiotensin I-converting enzyme gene polymorphisms on gastric cancer risks in Japan. Cancer Epidemiol Biomarkers Prev, 15, 1929-34.
  22. Toma M, Cimponeriu D, Apostol P, et al (2009). Lack of association between ACE ID polymorphism and colorectal cancer in Romanian patients. Chirurgia (Bucur), 104, 553-6.
  23. van der Knaap R, Siemes C, Coebergh JW, et al (2008). Reninangiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer: the Rotterdam Study. Cancer, 112, 748-57.
  24. Yoshiji H, Kuriyama S, Fukui H (2002a). Perindopril: possible use in cancer therapy. Anticancer Drug, 13, 221-8.
  25. Yoshiji H, Kuriyama S, Fukui H (2002b). Angiotensin-Iconverting enzyme inhibitors may be an alternative anti-angiogenic strategy in the treatment of liver fibrosis and hepatocellular carcinoma. Possible role of vascular endothelial growth factor. Tumour Biol, 23, 348-56.
  26. Yuan F, Zhang LS, Li HY, et al (2013). Influence of angiotensin I-converting enzyme gene polymorphism on hepatocellular carcinoma risk in China. Dna Cell Biol, 32, 268-73.
  27. Zhang Y, He J, Deng Y, et al (2011). The insertion/deletion (I/D). polymorphism in the Angiotensin-converting enzyme gene and cancer risk: a meta-analysis. BMC Med Genet, 12, 159.
  28. Zhou L, Hu Y, Gao HF, et al (2010). Polymorphism of angiotensin I-converting enzyme gene in peripheral blood of colon cancer patients(chinese). Cancer Res Prev Treat, 37, 1040-3.

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