Association between captopril, other antihypertensive drugs and risk of prostate cancer

Ronquist, Gunnar; Rodrı́guez, Luis A. Garcı́a; Ruigómez, Ana; Johansson, Saga; Wallander, Mari‐Ann; Frithz, Göran; Svärdsudd, Kurt

doi:10.1002/pros.10294

Cited by 106 publications

(110 citation statements)

References 26 publications

(30 reference statements)

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“…Other epidemiologic studies have been performed to investigate the association between ACE inhibitors or AT1R antagonists and cancer; however, 11,[14][15][16] or prostate cancer 17,18 after adjusting for covariates (Table 2). Older studies reported protective effects.…”

Section: Discussionmentioning

confidence: 99%

“…10 In contrast, several other studies could not confirm those results. [11][12][13][14][15][16][17][18][19] Two randomized clinical trials reported nonsignificantly increased risks of malignancy for users of ACE inhibitors, but the follow-up of approximately 3 years was limited. 20 Currently, the association between RAS inhibitors and cancer risk remains inconclusive.…”

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confidence: 99%

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Renin‐angiotensin system inhibitors, angiotensin I‐converting enzyme gene insertion/deletion polymorphism, and cancer

Knaap

Siemes

Coebergh

et al. 2008

Cancer

119

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BACKGROUND. Angiotensin I‐converting enzyme (ACE) inhibitors, angiotensin II antagonists, and the ACE insertion/deletion (I/D) gene polymorphism all influence serum angiotensin II action. Because angiotensin II levels have been associated with cancer, the objective of the current epidemiologic study was to investigate whether renin‐angiotensin system inhibitors and/or ACE genotypes were associated with an altered risk of colorectal, lung, breast, and prostate cancer. METHODS. Data were obtained from the Rotterdam Study, a population‐based, prospective cohort study with 7983 participants. Participants who had a history of 1 of the cancers of interest (n = 216) or who had a medication history <6 months (n = 88) were excluded, leaving 7679 participants, of whom the ACE genotypes could be assessed in 6670 individuals. The mean follow‐up was 9.6 years, during which 730 incident cancers occurred. The effect of medication, ACE I/D genotypes, and their interaction on cancer risk and progression was studied by using Cox proportional hazard models. RESULTS. Carriers of the high‐activity genotype DD had an increased risk of breast cancer compared with low‐activity II/ID genotype carriers (hazard ratio [HR], 1.47; 95% confidence interval [95% CI], 1.05–2.04), but no association was demonstrated for other cancers. DD carriers who were exposed to long‐term and high‐dose medication were at lower risk for cancer (HR, 0.28; 95% CI, 0.10–0.79). Short‐term, high‐dose users were at risk for colorectal cancer progression in the II/ID stratum (HR, 3.83; 95% CI, 1.67–8.79). CONCLUSIONS. Renin‐angiotensin system‐inhibiting drugs seemed to protect against cancer in individuals with the DD genotype, which was associated with high levels of ACE. Cancer 2008. © 2008 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Renin‐angiotensin system inhibitors, angiotensin I‐converting enzyme gene insertion/deletion polymorphism, and cancer

Knaap

Siemes

Coebergh

et al. 2008

Cancer

119

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“…Two of the cohort studies were used only in the subgroup analyses because they shared a study population (Appendix 2). 22,34 We contacted the authors of six articles to ask for the combined estimates for total drug users; 5,19,[21][22][23]34 the authors of three articles provided these adjusted estimates. 19,21,23 The outcome measures were unsuitable for meta-analysis in two case-control studies; 11,28 we therefore used data from 2 × 2 tables to recalculate the crude estimates.…”

Section: Articles Screened N = 3735mentioning

confidence: 99%

Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies

Yoon¹,

Yang²,

Jeon³

et al. 2011

CMAJ

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R ecent meta-analyses have shown a possible increased risk of cancer associated with angiotensin-receptor blockers used alone or combined with angiotensin-convertingenzyme (ACE) inhibitors.1,2 Despite the strong internal validity of randomized controlled trials (RCTs) used in prior meta-analyses, it is difficult to interpret these results because of the short duration of follow-up for cancer detection.3 A previous retrospective cohort study with a mean follow-up of 6.6 years showed that the use of ACE inhibitors was associated with a significantly de creased risk of overall cancer, and cancer of the lung, breast and female reproductive organs and smoking-related cancers. 4 Despite the inconsistent results reported by previous observational studies regarding this issue, 4−35 we conducted a meta-analysis of cohort and casecontrol studies to assess the association between use of these medications and the risk of cancer. Methods Literature searchWe searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library up to January 2011 using common keywords related to ACE inhibitors, angiotensin-receptor blockers and cancer. The search terms were as follows: "angiotensin-converting enzyme inhibitor" or "angiotensin receptor blocker" or trade names of the medications AND "cancer" or "carcinoma" or "neoplasm" or "malignancy" or names of specific types of cancer. (For details about the search strategy, see Appendix 1, at www.cmaj.ca /lookup /suppl/doi:10.1503 /cmaj .101497 /-/DC1.) We also reviewed the bibliographies of relevant articles to identify additional publications. Studies were restricted to those involving humans. We performed a meta-analysis of observational studies to assess the association.

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“…While Ang II has been used in cancer to enable better accessibility of chemotherapeutic drugs to the tumour (Noguchi et al, 1988), Ang II blockers and ACE inhibitors have nevertheless been shown to reduce tumour size, angiogenesis and metastasis (Fujita et al, 2002;Uemura et al, 2005), although the suggestion that long-term use of angiotensin converting enzyme (ACE) inhibitors in patients may limit the development of cancer (Lever et al, 1998) has been questioned (Li et al, 2003;Ronquist et al, 2004). Tahmasebi et al (1998) showed the transcription of (pro)renin in fibroblasts and myoepithelial cells in normal and abnormal breast tissue, suggesting the existence of a tRAS within the breast.…”

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confidence: 99%

Localisation of renin-angiotensin system (RAS) components in breast

et al. 2006

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Angiotensin II has mitogenic and angiogenic effects and its receptors are widespread, particularly in epithelial tissue. Tissue renin angiotensin systems (tRASs) may be a local source of angiotensin II that has specific paracrine functions. To investigate the presence of a tRAS in normal human breast and tumours. Immunocytochemistry, and quantitative RT -PCR was used to establish: (i) the presence and localisation of RAS components, (ii) the possibility of their involvement in cancer. (1) mRNA coding for angiotensinogen, prorenin, angiotensin converting enzyme (ACE), and both AT1 and AT2 receptors was demonstrated in normal and diseased breast tissues. (2) (pro)renin was identified in epithelial cells in both normal and diseased tissue, but in invasive carcinoma, its distribution was mostly confined to fibroblasts or could not be detected at all. (3) Angiotensin converting enzyme was shown in epithelial cells in both normal and malignant tissue. The results are consistent with the hypothesis that a tRAS is present in the breast, and is disrupted in invasive cancer.

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Association between captopril, other antihypertensive drugs and risk of prostate cancer

Abstract: No clear association was apparent between the use of antihypertensive drugs and prostate cancer. However, specific focus on users of captopril showed a lower risk of subsequent prostate cancer. Further research is needed to explore this association.

Cited by 106 publications

References 26 publications

Renin‐angiotensin system inhibitors, angiotensin I‐converting enzyme gene insertion/deletion polymorphism, and cancer

Renin‐angiotensin system inhibitors, angiotensin I‐converting enzyme gene insertion/deletion polymorphism, and cancer

Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers and cancer risk: a meta-analysis of observational studies

Localisation of renin-angiotensin system (RAS) components in breast

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