Skip to main content

Advertisement

SpringerLink
Log in

Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy and colorectal cancer: a systematic review and meta-analysis

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

We aim to investigate the association between angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) therapy and colorectal cancer (CRC) by conducting a systematic review with meta-analysis.

Methods

Literature was searched on PubMed, Scopus, and the Cochrane library to identify relevant studies evaluating ACEIs/ARBs therapy and risk of CRC incidence or survival of CRC patients. Pooled risk ratio (RR) with 95 % confidence intervals was calculated for the association between ACEIs/ARBs and CRC risk and mortality.

Results

Eleven observational studies were included in the systematic review. A meta-analysis of six studies totaling 113,048 individuals indicated a 6 % decreased risk of CRC in ACEIs/ARBs users compared to non-users (95 % CI 0.89–0.98). In the four case–control studies, individuals using ACEIs/ARBs were associated with a 6 % decreased risk of CRC (95 % CI 0.90–0.99). The meta-analysis of three studies investigating the relationship between ACEIs/ARBs and survival of CRC did not show a significantly decreased mortality in ACEIs/ARBs users (RR 0.81, 95 % CI 0.60–1.09). Seven studies evaluated the dose–response relationship between ACEIs/ARBs therapy and CRC, and two of them showed that the association was related to longer duration and higher dose.

Conclusions

CEIs/ARBs therapy might be associated with a reduce risk of CRC development, but whether use of these medications improves the outcomes of CRC remains unknown. Large-scale and more robust studies are needed to further explore this association.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Andrieu N, Launoy G, Guillois R, Ory-Paoletti C, Gignoux M (2003) Familial relative risk of colorectal cancer: a population-based study. Eur J Cancer 39:1904–1911

    Article  CAS  PubMed  Google Scholar 

  3. Klabunde CN, Lanier D, Nadel MR, McLeod C, Yuan G et al (2009) Colorectal cancer screening by primary care physicians: recommendations and practices, 2006-2007. Am J Prev Med 37:8–16

    Article  PubMed Central  PubMed  Google Scholar 

  4. Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM et al (1993) Reducing mortality from colorectal cancer by screening for fecal occult blood. Minn Colon Cancer Control Study N Engl J Med 328:1365–1371

    CAS  Google Scholar 

  5. Vogelaar I, van Ballegooijen M, Schrag D, Boer R, Winawer SJ et al (2006) How much can current interventions reduce colorectal cancer mortality in the US? Mortality projections for scenarios of risk-factor modification, screening, and treatment. Cancer 107:1624–1633

    Article  PubMed  Google Scholar 

  6. Force USPST (2008) Screening for colorectal cancer: US preventive services task force recommendation statement. Ann Intern Med 149:627–637

    Article  Google Scholar 

  7. Lever AF, Hole DJ, Gillis CR, McCallum IR, McInnes GT et al (1998) Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet 352:179–184

    Article  CAS  PubMed  Google Scholar 

  8. Huang CC, Chan WL, Chen YC, Chen TJ, Lin SJ et al (2011) Angiotensin II receptor blockers and risk of cancer in patients with systemic hypertension. Am J Cardiol 107:1028–1033

    Article  CAS  PubMed  Google Scholar 

  9. Mc Menamin UC, Murray LJ, Cantwell MM, Hughes CM (2012) Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cancer progression and survival: a systematic review. Cancer Causes Control 23:221–230

    Article  PubMed  Google Scholar 

  10. Friis S, Sorensen HT, Mellemkjaer L, McLaughlin JK, Nielsen GL et al (2001) Angiotensin-converting enzyme inhibitors and the risk of cancer: a population-based cohort study in Denmark. Cancer 92:2462–2470

    Article  CAS  PubMed  Google Scholar 

  11. Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC (2010) Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol 11:627–636

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Song M, Giovannucci EL (2014) Antihypertension and colorectal cancer prevention: getting two birds with one stone? J Natl Cancer Inst 106:djt438

    Article  PubMed  Google Scholar 

  13. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(264–269):W264

    Article  Google Scholar 

  14. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605

    Article  PubMed  Google Scholar 

  15. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  16. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed Central  PubMed  Google Scholar 

  17. Thornton A, Lee P (2000) Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol 53:207–216

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Kedika R, Patel M, Pena Sahdala HN, Mahgoub A, Cipher D et al (2011) Long-term use of angiotensin converting enzyme inhibitors is associated with decreased incidence of advanced adenomatous colon polyps. J Clin Gastroenterol 45:e12–e16

    Article  CAS  PubMed  Google Scholar 

  20. Engineer DR, Burney BO, Hayes TG, Garcia JM (2013) Exposure to ACEI/ARB and beta-blockers is associated with improved survival and decreased tumor progression and hospitalizations in patients with advanced colon cancer. Transl Oncol 6:539–545

    Article  PubMed Central  PubMed  Google Scholar 

  21. Holmes S, Griffith EJ, Musto G, Minuk GY (2013) Antihypertensive medications and survival in patients with cancer: a population-based retrospective cohort study. Cancer Epidemiol 37:881–885

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  23. Assimes TL, Elstein E, Langleben A, Suissa S (2008) Long-term use of antihypertensive drugs and risk of cancer. Pharmacoepidemiol Drug Saf 17:1039–1049

    Article  CAS  PubMed  Google Scholar 

  24. Azoulay L, Assimes TL, Yin H, Bartels DB, Schiffrin EL et al (2012) Long-term use of angiotensin receptor blockers and the risk of cancer. PLoS One 7:e50893

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Boudreau DM, Koehler E, Rulyak SJ, Haneuse S, Harrison R et al (2008) Cardiovascular medication use and risk for colorectal cancer. Cancer Epidemiol Biomark Prev 17:3076–3080

    Article  CAS  Google Scholar 

  26. Makar GA, Holmes JH, Yang YX (2014) Angiotensin-converting enzyme inhibitor therapy and colorectal cancer risk. J Natl Cancer Inst 106:djt374

    Article  PubMed Central  PubMed  Google Scholar 

  27. Cardwell CR, Mc Menamin UC, Hicks BM, Hughes C, Cantwell MM et al (2014) Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts. BMC Med 12:28

    Article  PubMed Central  PubMed  Google Scholar 

  28. Mansouri D, McMillan DC, Roxburgh CS, Crighton EM, Horgan PG (2013) The impact of aspirin, statins and ACE-inhibitors on the presentation of colorectal neoplasia in a colorectal cancer screening programme. Br J Cancer 109:249–256

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Bardou M, Barkun A, Martel M (2010) Effect of statin therapy on colorectal cancer. Gut 59:1572–1585

    Article  CAS  PubMed  Google Scholar 

  30. Dube C, Rostom A, Lewin G, Tsertsvadze A, Barrowman N et al (2007) The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the US preventive services task force. Ann Intern Med 146:365–375

    Article  PubMed  Google Scholar 

  31. Yasumaru M, Tsuji S, Tsujii M, Irie T, Komori M et al (2003) Inhibition of angiotensin II activity enhanced the antitumor effect of cyclooxygenase-2 inhibitors via insulin-like growth factor I receptor pathway. Cancer Res 63:6726–6734

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Greene AS, Amaral SL (2002) Microvascular angiogenesis and the renin-angiotensin system. Curr Hypertens Rep 4:56–62

    Article  PubMed  Google Scholar 

  34. George AJ, Thomas WG, Hannan RD (2010) The renin-angiotensin system and cancer: old dog, new tricks. Nat Rev Cancer 10:745–759

    Article  CAS  PubMed  Google Scholar 

  35. Kubota M, Shimizu M, Sakai H, Yasuda Y, Ohno T et al (2011) Renin-angiotensin system inhibitors suppress azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice. Biochem Biophys Res Commun 410:108–113

    Article  CAS  PubMed  Google Scholar 

  36. Shirakami Y, Shimizu M, Kubota M, Araki H, Tanaka T et al (2014) Chemoprevention of colorectal cancer by targeting obesity-related metabolic abnormalities. World J Gastroenterol 20:8939–8946

    PubMed Central  PubMed  Google Scholar 

  37. Neo JH, Ager EI, Angus PW, Zhu J, Herath CB et al (2010) Changes in the renin angiotensin system during the development of colorectal cancer liver metastases. BMC Cancer 10:134

    Article  PubMed Central  PubMed  Google Scholar 

  38. Wen SW, Ager EI, Neo J, Christophi C (2013) The renin angiotensin system regulates Kupffer cells in colorectal liver metastases. Cancer Biol Ther 14:720–727

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Luo Y, Ohmori H, Shimomoto T, Fujii K, Sasahira T et al (2011) Anti-angiotensin and hypoglycemic treatments suppress liver metastasis of colon cancer cells. Pathobiology 78:285–290

    Article  CAS  PubMed  Google Scholar 

  40. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

All authors have declared that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, Zhejiang, China

    Yi-Ning Dai, Jing-Hua Wang, Jin-Zhou Zhu, Jie-Qiong Lin, Chao-Hui Yu & You-Ming Li

Authors
  1. Yi-Ning Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jing-Hua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jin-Zhou Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie-Qiong Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chao-Hui Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. You-Ming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to You-Ming Li.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, YN., Wang, JH., Zhu, JZ. et al. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy and colorectal cancer: a systematic review and meta-analysis. Cancer Causes Control 26, 1245–1255 (2015). https://doi.org/10.1007/s10552-015-0617-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-015-0617-1

Keywords

Search

Navigation