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Association between polymorphisms of the renin–angiotensin system genes and breast cancer risk: a meta-analysis

  • Epidemiology
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Abstract

The renin–angiotensin system (RAS) has been considered to be implicated in the development of breast cancer. However, the results are inconsistent. In this study, we conducted a meta-analysis to assess the association between four polymorphisms, including angiotensin I-converting enzyme (ACE) I/D and A240T, angiotensin II type 1 receptor (AGTR1) A1166C and angiotensinogen (AGT) M235T polymorphisms, and breast cancer risk. Published literature from PubMed, ISI web of science, and Embase databases were retrieved. All studies evaluating the association between ACE I/D, ACE A240T, AGTR1 A1166C, or AGT M235T polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Ten studies (1,650 cases and 9,283 controls) on ACE I/D polymorphism, six studies (1,316 cases and 2,632 controls) on ACE A240T polymorphism, three studies (235 cases and 601 controls) on AGTR1 A1166C polymorphism, and two studies (273 cases and 3,547 controls) on AGT M235T polymorphism were included. Overall, the meta-analysis showed no significant association between I/D or A240T polymorphism and breast cancer risk in either genetic model. Further subgroup analysis by ethnicity also revealed non-significant association in Caucasian or Asian populations except for Africans (the statistically significant association for ACE I/D or A240T polymorphism in Africans derived from only one study). A marginally significant association was observed for AGTR1 A1166C polymorphism in Caucasians (CC vs. AA: OR = 0.31, 95% CI 0.10–0.99). In addition, there was a significant association between AGT M235T polymorphism and breast cancer risk in Caucasians (OR = 1.45, 95% CI 1.12–1.88). The present meta-analysis suggested that ACE I/D and A240T polymorphisms might not be a good predictor of breast cancer risk, while AGTR1 A1166C and AGT M235T polymorphisms might be implicated in the pathogenesis of breast cancer. Given the limited sample size, the findings warrant further investigation.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108

    Article  PubMed  Google Scholar 

  2. Travis RC, Reeves GK, Green J, Bull D, Tipper SJ, Baker K, Beral V, Peto R, Bell J, Zelenika D, Lathrop M, Million Women Study Collaborators (2010) Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study. Lancet 375(9732):2143–2151

    Article  PubMed  CAS  Google Scholar 

  3. Narod SA (2010) Genes, the environment, and breast cancer. Lancet 375(9732):2123–2124

    Article  PubMed  Google Scholar 

  4. Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M (2010) Genetic susceptibility to breast cancer. Mol Oncol 4(3):174–191

    Article  PubMed  CAS  Google Scholar 

  5. Eccles D, Tapper W (2010) The influence of common polymorphisms on breast cancer. Cancer Treat Res 155:15–32

    Article  PubMed  CAS  Google Scholar 

  6. Timmermans PB, Chiu AT, Herblin WF, Wong PC, Smith RD (1992) Angiotensin II receptor subtypes. Am J Hypertens 5(6 Pt 1):406–410

    PubMed  CAS  Google Scholar 

  7. Deshayes F, Nahmias C (2005) Angiotensin receptors: a new role in cancer? Trends Endocrinol Metab 16(7):293–299

    Article  PubMed  CAS  Google Scholar 

  8. Villard E, Tiret L, Visvikis S, Rakotovao R, Cambien F, Soubrier F (1996) Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis. Am J Hum Genet 58(6):1268–1278

    PubMed  CAS  Google Scholar 

  9. Sadoshima J, Aoki H, Izumo S (1997) Angiotensin II and serum differentially regulate expression of cyclins, activity of cyclin-dependent kinases, and phosphorylation of retinoblastoma gene product in neonatal cardiac myocytes. Circ Res 80(2):228–241

    PubMed  CAS  Google Scholar 

  10. Lever AF, Hole DJ, Gillis CR, McCallum IR, McInnes GT, MacKinnon PL, Meredith PA, Murray LS, Reid JL, Robertson JW (1998) Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet 352(9123):179–184

    Article  PubMed  CAS  Google Scholar 

  11. Célérier J, Cruz A, Lamandé N, Gasc JM, Corvol P (2002) Angiotensinogen and its cleaved derivatives inhibit angiogenesis. Hypertension 39(2):224–228

    Article  PubMed  Google Scholar 

  12. Gould AB, Green D (1971) Kinetics of the human renin and human substrate reaction. Cardiovasc Res 5(1):86–89

    Article  PubMed  CAS  Google Scholar 

  13. Niu W, Qi Y (2010) Association of the angiotensin II type I receptor gene +1166 A>C polymorphism with hypertension risk: evidence from a meta-analysis of 16474 subjects. Hypertens Res 33(11):1137–1143

    Article  PubMed  CAS  Google Scholar 

  14. Koh WP, Yuan JM, Van Den Berg D, Lee HP, Yu MC (2005) Polymorphisms in angiotensin II type 1 receptor and angiotensin I-converting enzyme genes and breast cancer risk among Chinese women in Singapore. Carcinogenesis 26(2):459–464

    Article  PubMed  CAS  Google Scholar 

  15. Koh WP, Yuan JM, Sun CL, van den Berg D, Seow A, Lee HP, Yu MC (2003) Angiotensin I-converting enzyme (ACE) gene polymorphism and breast cancer risk among Chinese women in Singapore. Cancer Res 63(3):573–578

    PubMed  CAS  Google Scholar 

  16. 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(20):6984–6987

    PubMed  CAS  Google Scholar 

  17. Yuan JM, Koh WP, Sun CL, Lee HP, Yu MC (2005) Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore. Carcinogenesis 26(8):1389–1394

    Article  PubMed  CAS  Google Scholar 

  18. González-Zuloeta Ladd AM, Arias Vásquez A, Sayed-Tabatabaei FA, Coebergh JW, Hofman A, Njajou O, Stricker B, van Duijn C (2005) Angiotensin-converting enzyme gene insertion/deletion polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14(9):2143–2146

    Article  PubMed  Google Scholar 

  19. Yaren A, Turgut S, Kursunluoglu R, Oztop I, Turgut G, Kelten C, Erdem E (2006) Association between the polymorphism of the angiotensin-converting enzyme gene and tumor size of breast cancer in premenopausal patients. Tohoku J Exp Med 210(2):109–116

    Article  PubMed  CAS  Google Scholar 

  20. Yaren A, Turgut S, Kursunluoglu R, Oztop I, Turgut G, Degirmencioglu S, Kelten C, Erdem E (2007) Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors. J Investig Med 55(5):255–261

    Article  PubMed  CAS  Google Scholar 

  21. van der Knaap R, Siemes C, Coebergh JW, van Duijn CM, Hofman A, Stricker BH (2008) Renin–angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer: the Rotterdam Study. Cancer 112(4):748–757

    Article  PubMed  Google Scholar 

  22. Alves Corrêa SA, Ribeiro de Noronha SM, Nogueira-de-Souza NC, Valleta de Carvalho C, Massad Costa AM, Juvenal Linhares J, Vieira Gomes MT, Guerreiro da Silva ID (2009) Association between the angiotensin-converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms and breast cancer among Brazilian women. J Renin Angiotensin Aldosterone Syst 10(1):51–58

    Article  PubMed  Google Scholar 

  23. Mendizábal-Ruiz AP, Morales JA, Castro Marti Nez X, Gutierrez Rubio SA, Valdez L, Vásquez-Camacho JG, Sanchez Corona J, Moran Moguel MC (2010) RAS polymorphisms in cancerous and benign breast tissue. J Renin Angiotensin Aldosterone Syst. doi: 10.1177/1470320310383735

  24. Namazi S, Monabati A, Ardeshir-Rouhani-Fard S, Azarpira N (2010) Association of angiotensin I converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms with breast cancer prognostic factors in Iranian population. Mol Carcinog 49(12):1022–1030

    Article  PubMed  CAS  Google Scholar 

  25. González-Zuloeta Ladd AM, Arias Vásquez A, Siemes C, Yazdanpanah M, Coebergh JW, Hofman A, Stricker BH, van Duijn CM (2007) Differential roles of Angiotensinogen and Angiotensin Receptor type 1 polymorphisms in breast cancer risk. Breast Cancer Res Treat 101(3):299–304

    Article  PubMed  Google Scholar 

  26. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  PubMed  CAS  Google Scholar 

  27. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748

    PubMed  CAS  Google Scholar 

  28. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    PubMed  CAS  Google Scholar 

  29. Ager EI, Neo J, Christophi C (2008) The renin–angiotensin system and malignancy. Carcinogenesis 29(9):1675–1684

    Article  PubMed  CAS  Google Scholar 

  30. Ruiter R, Visser LE, Van Duijn CM, Ch Stricker BH (2011) The ACE insertion/deletion polymorphism and risk of cancer, a review and meta-analysis of the literature. Curr Cancer Drug Targets 11(4):421–430

    Google Scholar 

  31. Röcken C, Lendeckel U, Dierkes J, Westphal S, Carl-McGrath S, Peters B, Krüger S, Malfertheiner P, Roessner A, Ebert MP (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(7):2526–2530

    Article  PubMed  Google Scholar 

  32. Ebert MP, Lendeckel U, Westphal S, Dierkes J, Glas J, Folwaczny C, Roessner A, Stolte M, Malfertheiner P, Röcken C (2005) The angiotensin I-converting enzyme gene insertion/deletion polymorphism is linked to early gastric cancer. Cancer Epidemiol Biomarkers Prev 14(12):2987–2989

    Article  PubMed  CAS  Google Scholar 

  33. Goto Y, Ando T, Nishio K, Ishida Y, Kawai S, Goto H, Hamajima N (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(4):464–467

    PubMed  Google Scholar 

  34. Sugimoto M, Furuta T, Shirai N, Ikuma M, Sugimura H, Hishida A (2006) Influences of chymase and angiotensin I-converting enzyme gene polymorphisms on gastric cancer risks in Japan. Cancer Epidemiol Biomarkers Prev 15(10):1929–1934

    Article  PubMed  CAS  Google Scholar 

  35. Röcken C, Neumann K, Carl-McGrath S, Lage H, Ebert MP, Dierkes J, Jacobi CA, Kalmuk S, Neuhaus P, Neumann U (2007) The gene polymorphism of the angiotensin I-converting enzyme correlates with tumor size and patient survival in colorectal cancer patients. Neoplasia 9(9):716–722

    Article  PubMed  Google Scholar 

  36. 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(6):1065–1068

    PubMed  CAS  Google Scholar 

  37. Toma M, Cimponeriu D, Apostol P, Stavarachi M, Cojocaru M, Belusică L, Crăciun AM, Radu I, Gavrilă L (2009) Lack of association between ACE ID polymorphism and colorectal cancer in Romanian patients. Chirurgia (Bucur) 104(5):553–556

    CAS  Google Scholar 

  38. Cheon KT, Choi KH, Lee HB, Park SK, Rhee YK, Lee YC (2000) Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with lung cancer. Lung 178(6):351–360

    Article  PubMed  CAS  Google Scholar 

  39. Nacak M, Nacak I, Sanli M, Ozkur M, Pektaş M, Aynacioğlu AS (2010) Association of angiotensin converting enzyme gene insertion/deletion polymorphism with lung cancer in Turkey. Cancer Genet Cytogenet 198(1):22–26

    Article  PubMed  CAS  Google Scholar 

  40. Medeiros R, Vasconcelos A, Costa S, Pinto D, Lobo F, Morais A, Oliveira J, Lopes C (2004) Linkage of angiotensin I-converting enzyme gene insertion/deletion polymorphism to the progression of human prostate cancer. J Pathol 202(3):330–335

    Article  PubMed  CAS  Google Scholar 

  41. Yigit B, Bozkurt N, Narter F, Yilmaz H, Yucebas E, Isbir T (2007) Effects of ACE I/D polymorphism on prostate cancer risk, tumor grade and metastatis. Anticancer Res 27(2):933–936

    PubMed  CAS  Google Scholar 

  42. Sierra Díaz E, Sánchez Corona J, Rosales Gómez RC, Gutierrez Rubio SA, Vázquez Camacho JG, Solano Moreno H, Morán Moguel MC (2009) Angiotensin-converting enzyme insertion/deletion and angiotensin type 1 receptor A1166C polymorphisms as genetic risk factors in benign prostatic hyperplasia and prostate cancer. J Renin Angiotensin Aldosterone Syst 10(4):241–246

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Maternal and Child Health Care, School of Public Health, Shandong University, **an, 250012, China

    Bo **, Weina Liu & Jun Li

  2. Institute of Toxicology, School of Public Health, Shandong University, **an, 250012, China

    Tao Zeng

  3. Department of General Surgery, The Second Affiliated Hospital of Nan Chang University, Nanchang, 330006, China

    Liu Liu

  4. Graduate School, Peking Union Medical College, Bei**g, 100730, China

    Yajun Liang & Yuehua Hu

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Correspondence to Jun Li.

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**, B., Zeng, T., Liu, L. et al. Association between polymorphisms of the renin–angiotensin system genes and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 130, 561–568 (2011). https://doi.org/10.1007/s10549-011-1602-3

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