Skip to main content
Erschienen in: Cancer Causes & Control 12/2011

01.12.2011 | Brief report

Angiotensin converting enzyme inhibitors and hepatocellular carcinoma incidence in the General Practice Research Database

verfasst von: Alex J. Walker, Joe West, Matthew J. Grainge, Tim R. Card

Erschienen in: Cancer Causes & Control | Ausgabe 12/2011

Einloggen, um Zugang zu erhalten

Abstract

Objective

Laboratory findings demonstrate anticancer effects of angiotensin converting enzyme (ACE) inhibitors, including anti-angiogenic activity and inhibition of liver cancer growth in rodent models. Small studies in humans indicate potential for therapeutic anticancer effects and warrant further larger studies.

Methods

A case–control study using the General Practice Research Database examined whether prior ACE inhibitor usage was associated with a reduction in incidence of hepatocellular carcinoma (HCC).

Results

Two hundred twenty-four HCC cases were identified, each matched to up to 10 controls by age, sex, and general practice. The data show that HCC is associated with a small, nonsignificant increase in prior use of ACE inhibitors (OR = 1.16, CI = 0.67–2.00). ACE inhibitor use was 7.1% (of 224) in cases and 5.9% (of 2,313) in controls. No significant effects were found when investigating the effect of dose and exposure duration.

Conclusions

We found no clear protective effect of ever or long term use of ACE inhibitors against the development of HCC. Our study suggests that it is unlikely that this class of drugs will be a clinically useful cancer chemoprevention therapy.
Literatur
1.
Zurück zum Zitat West J, Wood H, Logan RF, Quinn M, Aithal GP (2006) Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001. Br J Cancer 94:1751–1758PubMedCrossRef West J, Wood H, Logan RF, Quinn M, Aithal GP (2006) Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001. Br J Cancer 94:1751–1758PubMedCrossRef
2.
Zurück zum Zitat El-Serag HB, Marrero JA, Rudolph L, Reddy KR (2008) Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology 134:1752–1763PubMedCrossRef El-Serag HB, Marrero JA, Rudolph L, Reddy KR (2008) Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology 134:1752–1763PubMedCrossRef
3.
Zurück zum Zitat Kumagi T, Hiasa Y, Hirschfield GM (2009) Hepatocellular carcinoma for the non-specialist. BMJ 339:b5039PubMedCrossRef Kumagi T, Hiasa Y, Hirschfield GM (2009) Hepatocellular carcinoma for the non-specialist. BMJ 339:b5039PubMedCrossRef
4.
Zurück zum Zitat Yang ZF, Poon RT (2008) Vascular changes in hepatocellular carcinoma. Anat Rec 291:721–734CrossRef Yang ZF, Poon RT (2008) Vascular changes in hepatocellular carcinoma. Anat Rec 291:721–734CrossRef
5.
Zurück zum Zitat Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390PubMedCrossRef Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390PubMedCrossRef
6.
Zurück zum Zitat Volpert OV, Ward WF, Lingen MW et al (1996) Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats. J Clin Invest 98:671–679PubMedCrossRef Volpert OV, Ward WF, Lingen MW et al (1996) Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats. J Clin Invest 98:671–679PubMedCrossRef
7.
Zurück zum Zitat Yoshiji H, Kuriyama S, Kawata M et al (2001) The angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth and angiogenesis: possible role of the vascular endothelial growth factor. Clin Cancer Res 7:1073–1078PubMed Yoshiji H, Kuriyama S, Kawata M et al (2001) The angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth and angiogenesis: possible role of the vascular endothelial growth factor. Clin Cancer Res 7:1073–1078PubMed
8.
Zurück zum Zitat Yanase K, Yoshiji H, Ikenaka Y et al (2007) Synergistic inhibition of hepatocellular carcinoma growth and hepatocarcinogenesis by combination of 5-fluorouracil and angiotensin-converting enzyme inhibitor via anti-angiogenic activities. Oncol Rep 17:441–446PubMed Yanase K, Yoshiji H, Ikenaka Y et al (2007) Synergistic inhibition of hepatocellular carcinoma growth and hepatocarcinogenesis by combination of 5-fluorouracil and angiotensin-converting enzyme inhibitor via anti-angiogenic activities. Oncol Rep 17:441–446PubMed
9.
Zurück zum Zitat Noguchi R, Yoshiji H, Kuriyama S et al (2003) Combination of interferon-beta and the angiotensin-converting enzyme inhibitor, perindopril, attenuates murine hepatocellular carcinoma development and angiogenesis. Clin Cancer Res 9:6038–6045PubMed Noguchi R, Yoshiji H, Kuriyama S et al (2003) Combination of interferon-beta and the angiotensin-converting enzyme inhibitor, perindopril, attenuates murine hepatocellular carcinoma development and angiogenesis. Clin Cancer Res 9:6038–6045PubMed
10.
Zurück zum Zitat Yoshiji H, Kuriyama S, Noguchi R et al (2005) Combination of interferon-beta and angiotensin-converting enzyme inhibitor, perindopril, attenuates the murine liver fibrosis development. Liver Int 25:153–161PubMedCrossRef Yoshiji H, Kuriyama S, Noguchi R et al (2005) Combination of interferon-beta and angiotensin-converting enzyme inhibitor, perindopril, attenuates the murine liver fibrosis development. Liver Int 25:153–161PubMedCrossRef
11.
Zurück zum Zitat Yoshiji H, Kuriyama S, Noguchi R et al (2006) Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities. Oncol Rep 15:155–159PubMed Yoshiji H, Kuriyama S, Noguchi R et al (2006) Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities. Oncol Rep 15:155–159PubMed
12.
Zurück zum Zitat Yoshiji H, Kuriyama S, Noguchi R et al (2005) Combination of vitamin K2 and the angiotensin-converting enzyme inhibitor, perindopril, attenuates the liver enzyme-altered preneoplastic lesions in rats via angiogenesis suppression. J Hepatol 42:687–693PubMedCrossRef Yoshiji H, Kuriyama S, Noguchi R et al (2005) Combination of vitamin K2 and the angiotensin-converting enzyme inhibitor, perindopril, attenuates the liver enzyme-altered preneoplastic lesions in rats via angiogenesis suppression. J Hepatol 42:687–693PubMedCrossRef
13.
Zurück zum Zitat Yoshiji H, Noguchi R, Toyohara M et al (2009) Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. J Hepatol 51:315–321PubMedCrossRef Yoshiji H, Noguchi R, Toyohara M et al (2009) Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. J Hepatol 51:315–321PubMedCrossRef
14.
Zurück zum Zitat Yoshiji H, Noguchi R, Yamazaki M et al (2007) Combined treatment of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis. World J Gastroenterol 13:3259–3261PubMedCrossRef Yoshiji H, Noguchi R, Yamazaki M et al (2007) Combined treatment of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis. World J Gastroenterol 13:3259–3261PubMedCrossRef
15.
Zurück zum Zitat Herrett E, Thomas SL, Schoonen WM, Smeeth L, Hall AJ (2010) Validation and validity of diagnoses in the General Practice Research Database: a systematic review. Br J Clin Pharmacol 69:4–14PubMedCrossRef Herrett E, Thomas SL, Schoonen WM, Smeeth L, Hall AJ (2010) Validation and validity of diagnoses in the General Practice Research Database: a systematic review. Br J Clin Pharmacol 69:4–14PubMedCrossRef
16.
Zurück zum Zitat Jick H, Jick SS, Derby LE (1991) Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. BMJ 302:766–768PubMedCrossRef Jick H, Jick SS, Derby LE (1991) Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. BMJ 302:766–768PubMedCrossRef
17.
Zurück zum Zitat Jick SS, Kaye JA, Vasilakis-Scaramozza C et al (2003) Validity of the general practice research database. Pharmacotherapy 23:686–689PubMedCrossRef Jick SS, Kaye JA, Vasilakis-Scaramozza C et al (2003) Validity of the general practice research database. Pharmacotherapy 23:686–689PubMedCrossRef
18.
Zurück zum Zitat Meal A, Leonardi-Bee J, Smith C, Hubbard R, Bath-Hextall F (2008) Validation of THIN data for non-melanoma skin cancer. Qual Prim Care 16:49–52PubMed Meal A, Leonardi-Bee J, Smith C, Hubbard R, Bath-Hextall F (2008) Validation of THIN data for non-melanoma skin cancer. Qual Prim Care 16:49–52PubMed
19.
Zurück zum Zitat Sjöberg T, García Rodríguez LA, Lindblad M (2007) Angiotensin-converting enzyme inhibitors and risk of esophageal and gastric cancer: a nested case-control study. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc 5: 1160–1166.e1 Sjöberg T, García Rodríguez LA, Lindblad M (2007) Angiotensin-converting enzyme inhibitors and risk of esophageal and gastric cancer: a nested case-control study. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc 5: 1160–1166.e1
20.
Zurück zum Zitat Suissa S (2008) Immeasurable time bias in observational studies of drug effects on mortality. Am J Epidemiol 168:329–335PubMedCrossRef Suissa S (2008) Immeasurable time bias in observational studies of drug effects on mortality. Am J Epidemiol 168:329–335PubMedCrossRef
Metadaten
Titel
Angiotensin converting enzyme inhibitors and hepatocellular carcinoma incidence in the General Practice Research Database
verfasst von
Alex J. Walker
Joe West
Matthew J. Grainge
Tim R. Card
Publikationsdatum
01.12.2011
Verlag
Springer Netherlands
Erschienen in
Cancer Causes & Control / Ausgabe 12/2011
Print ISSN: 0957-5243
Elektronische ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-011-9837-1

Weitere Artikel der Ausgabe 12/2011

Cancer Causes & Control 12/2011 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.