PURPOSE: The proposed mechanism by which angiotensin II and angiotensin II-receptor blockers (ARBs) may influence the risk of cancer and the literature describing a possible causal relationship between ARB use and specific types of cancers are reviewed. SUMMARY: A number of cell-signaling pathways have been identified to establish a relationship between angiotensin II and cancer. Preclinical data support agonism of the angiotensin type-1 receptor by angiotensin II and unopposed stimulation of the angiotensin type-2 receptor as possible causes of proliferative and angiogenic processes. Results from a large meta-analysis suggested that ARB use is associated with a modest increase in risk of new cancer incidence. The publication of that meta-analysis led to subsequent large population analyses. A comprehensive literature review was conducted to identify studies evaluating the relationships among angiotensin II, ARBs, cancer, and malignancy. Preclinical studies evaluating the effects of angiotensin II and ARBs on proliferation and angiogenesis were selected to review how the renin-angiotensin system is involved in cellular proliferation and growth. Human studies evaluating the role of ARBs in specific types of cancer were also analyzed. The literature review found limited patient-specific data in humans to support the association. The Food and Drug Administration has concluded that there is no evidence of an increased risk of cancer with ARBs. CONCLUSION: At this time there is insufficient evidence to conclude that ARBs increase the risk of cancer. Blockade of the angiotensin system through both AT(1) and AT(2) receptors may have a protective effect against malignancy.
PURPOSE: The proposed mechanism by which angiotensin II and angiotensin II-receptor blockers (ARBs) may influence the risk of cancer and the literature describing a possible causal relationship between ARB use and specific types of cancers are reviewed. SUMMARY: A number of cell-signaling pathways have been identified to establish a relationship between angiotensin II and cancer. Preclinical data support agonism of the angiotensin type-1 receptor by angiotensin II and unopposed stimulation of the angiotensin type-2 receptor as possible causes of proliferative and angiogenic processes. Results from a large meta-analysis suggested that ARB use is associated with a modest increase in risk of new cancer incidence. The publication of that meta-analysis led to subsequent large population analyses. A comprehensive literature review was conducted to identify studies evaluating the relationships among angiotensin II, ARBs, cancer, and malignancy. Preclinical studies evaluating the effects of angiotensin II and ARBs on proliferation and angiogenesis were selected to review how the renin-angiotensin system is involved in cellular proliferation and growth. Human studies evaluating the role of ARBs in specific types of cancer were also analyzed. The literature review found limited patient-specific data in humans to support the association. The Food and Drug Administration has concluded that there is no evidence of an increased risk of cancer with ARBs. CONCLUSION: At this time there is insufficient evidence to conclude that ARBs increase the risk of cancer. Blockade of the angiotensin system through both AT(1) and AT(2) receptors may have a protective effect against malignancy.