Association of ACEIs/ARBs therapy with digestive system neoplasms: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LONG Linjing , CAO Guoli , LI Yuting ,  TANG Shaohui

Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, P.R.China;

Corresponding author：

TANG Shaohui, Email: tangshaohui205@163.com

Keywords：

Digestive system neoplasms; Colorectal cancer; Liver cancer; Gastric cancer; Pancreatic cancer; ACEI; ARB; Meta-analysis

DOI：

10.7507/1672-2531.201703036

Video：

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ObjectiveTo systematically review the association between angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) therapy and digestive system neoplasms.MethodsPubMed, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP and CBM databases were searched from inception to February 2017 to collect studies about ACEIs/ARBs therapy and risk of digestive system neoplasms or survival of digestive system neoplasms patients. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias of included studies, then meta-analysis was performed using Stata 12.0 software.ResultsA total of 21 articles including 32 studies were included. The results of meta-analysis showed that ACEIs/ARBs therapy could reduce the risk of colorectal cancer (OR=0.92, 95%CI 0.86 to 0.99, P=0.023), but there were no relationships between ACEIs/ARBs therapy and the risk of liver cancer or gastric cancer. ACEIs/ARBs therapy could improve the survival of colorectal cancer patients (HR=0.79, 95%CI 0.63 to 0.98, P=0.031), but there was no association between ACEIs/ARBs therapy and the survival of pancreatic cancer patients (HR=0.75, 95%CI 0.50 to 1.13, P=0.165).ConclusionACEIs/ARBs therapy may reduce the risk of colorectal cancer, as well as improve the survival of colorectal cancer patients, but there are no significant relationships between ACEIs/ARBs therapy and the risk or the survival of other digestive system neoplasms, such as liver cancer, gastric cancer and pancreatic cancer. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.

Citation： LONG Linjing, CAO Guoli, LI Yuting, TANG Shaohui. Association of ACEIs/ARBs therapy with digestive system neoplasms: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(9): 1051-1059. doi: 10.7507/1672-2531.201703036 Copy

1.	房静远. 中国大肠肿瘤筛查、早诊早治和综合预防共识意见. 胃肠病学和肝病学杂志, 2011, 20(11): 979-995.
2.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. Ca-Cancer J Clin, 2016, 66(2): 115-132.
3.	Van der Knaap R, Siemes C, Coebergh JW, et al. Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer. Cancer, 2008, 112(4): 748-757.
4.	Engineer DR, Burney BO, Hayes TG, et al. Exposure to ACEI/ARB and β-Blockers is associated with improved survival and decreased tumor progression and hospitalizations in patients with advanced colon cancer. Transl Oncol, 2013, 6(5): 539-545.
5.	Bhaskaran K, Douglas I, Evans S, et al. Angiotensin receptor blockers and risk of cancer: cohort study among people receiving antihypertensive drugs in UK General Practice Research Database. BMJ, 2012, 344: e2697.
6.	Walker AJ, West J, Grainge MJ, et al. Angiotensin converting enzyme inhibitors and hepatocellular carcinoma incidence in the General Practice Research Database. Cancer Causes Control, 2011, 22(12): 1743-1747.
7.	Wang KL, Liu CJ, Chao TF, et al. Long-term use of angiotensin II receptor blockers and risk of cancer: a population-based cohort analysis. Int J Cardiol, 2013, 167(5): 2162-2166.
8.	Pasternak B, Svanstrom H, Callreus T, et al. Use of angiotensin receptor blockers and the risk of cancer. Circulation, 2011, 123(16): 1729-1736.
9.	Assimes TL, Elstein E, Langleben A, et al. Long-term use of antihypertensive drugs and risk of cancer. Pharmacoepidemiol Drug Saf, 2008, 17(11): 1039-1049.
10.	Boudreau DM, Koehler E, Rulyak SJ, et al. Cardiovascular medication use and risk for colorectal cancer. Cancer Epidemiol Biomarkers Prev, 2008, 17(11): 3076-3080.
11.	Azoulay L, Assimes TL, Yin H, et al. Long-term use of angiotensin receptor blockers and the risk of cancer. PLoS One, 2012, 7(12): 50893.
12.	Mansouri D, Mcmillan DC, Roxburgh CSD, et al. The impact of aspirin, statins and ACE-inhibitors on the presentation of colorectal neoplasia in a colorectal cancer screening programme. Brit J Cancer, 2013, 109(1): 249-256.
13.	Makar GA, Holmes JH, Yang YX. Angiotensin-converting enzyme inhibitor therapy and colorectal cancer risk. J Natl Cancer Inst, 2014, 106(2): 374.
14.	Hallas J, Christensen R, Andersen M, et al. Long term use of drugs affecting the renin-angiotensin system and the risk of cancer: a population-based case-control study. Br J Clin Pharmacol, 2012, 74(1): 180-188.
15.	Fujimoto M, Kanou M, Hosomi K, et al. Angiotensin receptor blockers and the risk of cancer: data mining of a spontaneous reporting database and a claims database. Int J Clin Pharmacol Ther, 2017, 55(4):295-303.
16.	Sjöberg T, García Rodríguez LA, Lindblad M. Angiotensin-converting enzyme inhibitors and risk of esophageal and gastric cancer: a nested case-control study. Clin Gastroenterol Hepatol, 2007, 5(10): 1160-1166.
17.	Hagberg KW, Sahasrabuddhe VV, Mcglynn KA, et al. Does angiotensin-converting enzyme inhibitor and beta-blocker use reduce the risk of primary liver cancer? a case-control study using the UK Clinical Practice Research Datalink. Pharmacotherapy, 2016, 36(2): 187-195.
18.	Holmes S, Griffith EJ, Musto G, et al. Antihypertensive medications and survival in patients with cancer: a population-based retrospective cohort study. Cancer Epidemiol, 2013, 37(6): 881-885.
19.	Cardwell CR, Mc Menamin ÚC, Hicks BM, et al. Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts. BMC Med, 2014, 12(1): 28.
20.	Osumi H, Matsusaka S, Wakatsuki T, et al. Angiotensin II type-1 receptor blockers enhance the effects of bevacizumab-based chemotherapy in metastatic colorectal cancer patients. Mol Clin Oncol, 2015, 3(6): 1295-1300.
21.	Nakai Y, Isayama H, Ijichi H, et al. Inhibition of renin-angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine. Br J Cancer, 2010, 103(11): 1644-1648.
22.	Nakai Y, Isayama H, Sasaki T, et al. The inhibition of renin-angiotensin system in advanced pancreatic cancer: an exploratory analysis in 349 patients. J Cancer Res Clin, 2015, 141(5): 933-939.
23.	Tingle SJ. Role of anti-stromal polypharmacy in increasing survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. World J Gastrointest Pathophysiol, 2015, 6(4): 235.
24.	Mc Menamin ÚC, Murray LJ, Cantwell MM, et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cancer progression and survival: a systematic review. Cancer Causes Control, 2012, 23(2): 221-230.
25.	陈喜华, 刘景晶. 血管紧张素转化酶抑制剂与癌症关系的研究进展. 药物生物技术, 2010, 17(2): 172-176.
26.	Yasumaru M, Tsuji S, Tsujii M, et al. Inhibition of angiotensin II activity enhanced the antitumor effect of cyclooxygenase-2 inhibitors via insulin-like growth factor I receptor pathway. Cancer Res, 2003, 63(20): 6726-6734.
27.	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, 2015, 26(9): 1245-1255.

1. 房静远. 中国大肠肿瘤筛查、早诊早治和综合预防共识意见. 胃肠病学和肝病学杂志, 2011, 20(11): 979-995.
2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. Ca-Cancer J Clin, 2016, 66(2): 115-132.
3. Van der Knaap R, Siemes C, Coebergh JW, et al. Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer. Cancer, 2008, 112(4): 748-757.
4. Engineer DR, Burney BO, Hayes TG, et al. Exposure to ACEI/ARB and β-Blockers is associated with improved survival and decreased tumor progression and hospitalizations in patients with advanced colon cancer. Transl Oncol, 2013, 6(5): 539-545.
5. Bhaskaran K, Douglas I, Evans S, et al. Angiotensin receptor blockers and risk of cancer: cohort study among people receiving antihypertensive drugs in UK General Practice Research Database. BMJ, 2012, 344: e2697.
6. Walker AJ, West J, Grainge MJ, et al. Angiotensin converting enzyme inhibitors and hepatocellular carcinoma incidence in the General Practice Research Database. Cancer Causes Control, 2011, 22(12): 1743-1747.
7. Wang KL, Liu CJ, Chao TF, et al. Long-term use of angiotensin II receptor blockers and risk of cancer: a population-based cohort analysis. Int J Cardiol, 2013, 167(5): 2162-2166.
8. Pasternak B, Svanstrom H, Callreus T, et al. Use of angiotensin receptor blockers and the risk of cancer. Circulation, 2011, 123(16): 1729-1736.
9. Assimes TL, Elstein E, Langleben A, et al. Long-term use of antihypertensive drugs and risk of cancer. Pharmacoepidemiol Drug Saf, 2008, 17(11): 1039-1049.
10. Boudreau DM, Koehler E, Rulyak SJ, et al. Cardiovascular medication use and risk for colorectal cancer. Cancer Epidemiol Biomarkers Prev, 2008, 17(11): 3076-3080.
11. Azoulay L, Assimes TL, Yin H, et al. Long-term use of angiotensin receptor blockers and the risk of cancer. PLoS One, 2012, 7(12): 50893.
12. Mansouri D, Mcmillan DC, Roxburgh CSD, et al. The impact of aspirin, statins and ACE-inhibitors on the presentation of colorectal neoplasia in a colorectal cancer screening programme. Brit J Cancer, 2013, 109(1): 249-256.
13. Makar GA, Holmes JH, Yang YX. Angiotensin-converting enzyme inhibitor therapy and colorectal cancer risk. J Natl Cancer Inst, 2014, 106(2): 374.
14. Hallas J, Christensen R, Andersen M, et al. Long term use of drugs affecting the renin-angiotensin system and the risk of cancer: a population-based case-control study. Br J Clin Pharmacol, 2012, 74(1): 180-188.
15. Fujimoto M, Kanou M, Hosomi K, et al. Angiotensin receptor blockers and the risk of cancer: data mining of a spontaneous reporting database and a claims database. Int J Clin Pharmacol Ther, 2017, 55(4):295-303.
16. Sjöberg T, García Rodríguez LA, Lindblad M. Angiotensin-converting enzyme inhibitors and risk of esophageal and gastric cancer: a nested case-control study. Clin Gastroenterol Hepatol, 2007, 5(10): 1160-1166.
17. Hagberg KW, Sahasrabuddhe VV, Mcglynn KA, et al. Does angiotensin-converting enzyme inhibitor and beta-blocker use reduce the risk of primary liver cancer? a case-control study using the UK Clinical Practice Research Datalink. Pharmacotherapy, 2016, 36(2): 187-195.
18. Holmes S, Griffith EJ, Musto G, et al. Antihypertensive medications and survival in patients with cancer: a population-based retrospective cohort study. Cancer Epidemiol, 2013, 37(6): 881-885.
19. Cardwell CR, Mc Menamin ÚC, Hicks BM, et al. Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts. BMC Med, 2014, 12(1): 28.
20. Osumi H, Matsusaka S, Wakatsuki T, et al. Angiotensin II type-1 receptor blockers enhance the effects of bevacizumab-based chemotherapy in metastatic colorectal cancer patients. Mol Clin Oncol, 2015, 3(6): 1295-1300.
21. Nakai Y, Isayama H, Ijichi H, et al. Inhibition of renin-angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine. Br J Cancer, 2010, 103(11): 1644-1648.
22. Nakai Y, Isayama H, Sasaki T, et al. The inhibition of renin-angiotensin system in advanced pancreatic cancer: an exploratory analysis in 349 patients. J Cancer Res Clin, 2015, 141(5): 933-939.
23. Tingle SJ. Role of anti-stromal polypharmacy in increasing survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. World J Gastrointest Pathophysiol, 2015, 6(4): 235.
24. Mc Menamin ÚC, Murray LJ, Cantwell MM, et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cancer progression and survival: a systematic review. Cancer Causes Control, 2012, 23(2): 221-230.
25. 陈喜华, 刘景晶. 血管紧张素转化酶抑制剂与癌症关系的研究进展. 药物生物技术, 2010, 17(2): 172-176.
26. Yasumaru M, Tsuji S, Tsujii M, et al. Inhibition of angiotensin II activity enhanced the antitumor effect of cyclooxygenase-2 inhibitors via insulin-like growth factor I receptor pathway. Cancer Res, 2003, 63(20): 6726-6734.
27. 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, 2015, 26(9): 1245-1255.

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