Carcinogenicity of antihypertensive therapy

  • Ehud Grossman
  • Franz H. Messerli
  • Uri Goldbourt
Article

Abstract

Several studies have suggested that antihypertensive treatment may promote cancer through unknown mechanisms. Early retrospective studies implicated reserpine in breast cancer, but data from prospective studies and meta-analysis of several case-controlled studies showed only a weak association between reserpine and breast cancer which, although statistically significant, is of little clinical concern. Data from case-controlled studies and several cohort studies suggested an association between the use of a diuretic and the occurrence of renal cell cancer, particularly in women. A recent study showed an association between the use of a diuretic and the occurrence of colon cancer. Several prospective studies showed that treatment with atenolol may increase mortality from malignancy. However, other studies that analyzed data from several thousand patients could not confirm this association. In three prospective and a few case-controlled studies, angiotensin converting enzyme inhibitors were not associated with increased mortality from malignancy. In addition, a recent retrospective study showed that long-term use of angiotensin converting enzyme inhibitors had a protective effect against malignancy. Data from three large case-controlled studies and the combined data from eight randomized controlled studies and seven longitudinal studies showed a similar risk for malignancy among users and nonusers of calcium antagonists. Until further data from prospective clinical trials are available, we advise caution about longterm diuretic therapy in women. With regard to other antihypertensive drug classes, we suggest continuing the management of hypertension according to current treatment guidelines with little fear of any substantial cancer risk.

References and Recommended Reading

  1. 1.
    MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party. BMJ (Clin Res Ed) 1985, 291:97–104.Google Scholar
  2. 2.
    The Australian therapeutic trial in mild hypertension. Report by the management committee. Lancet 1980, 1:1261–1267.Google Scholar
  3. 3.
    Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992, 304:405–412.Google Scholar
  4. 4.
    SHEP Cooperative Research Group: Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991, 265:3255–3264.CrossRefGoogle Scholar
  5. 5.
    Staessen J, Bulpitt C, Clement D, et al.: Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly. BMJ 1989, 298:1552–1556.PubMedGoogle Scholar
  6. 6.
    Grossman E, Messerli FH, Boyko V, Goldbourt U: Is there an association between hypertension and cancer mortality. Am J Med 2002, In press.Google Scholar
  7. 7.
    Williams RR, Feinleib M, Connor RJ, Stegens NL: Case-control study of antihypertensive and diuretic use by women with malignant and benign breast lesions detected in a mammography screening program. J Natl Cancer Inst 1978, 61:327–335.PubMedGoogle Scholar
  8. 8.
    Fraser GE, Phillips RL, Beeson WL: Hypertension, antihypertensive medication and risk of renal carcinoma in California Seventh-Day Adventists. Int J Epidemiol 1990, 19:832–838.PubMedCrossRefGoogle Scholar
  9. 9.
    Grove JS, Nomura A, Severson RK, Stemmermann GN: The association of blood pressure with cancer incidence in a prospective study. Am J Epidemiol 1991, 134:942–947.PubMedGoogle Scholar
  10. 10.
    Suadicani P, Hein HO, Gyntelberg F: Is the use of antihypertensives and sedatives a major risk factor for colorectal cancer? Scand J Gastroenterol 1993, 28:475–481.PubMedGoogle Scholar
  11. 11.
    McLaughlin JK, Chow WH, Mandel JS, et al.: International renal-cell cancer study. VIII. Role of diuretics, other antihypertensive medications and hypertension. Int J Cancer 1995, 63:216–221.PubMedCrossRefGoogle Scholar
  12. 12.
    Chow WH, McLaughlin JK, Mandel JS, et al.: Risk of renal cell cancer in relation to diuretics, antihypertensive drugs, and hypertension. Cancer Epidemiol Biomarkers Prev 1995, 4:327–331.PubMedGoogle Scholar
  13. 13.
    Peeters PH, van Noord PA, Hoes AW, Grobbee DE: Hypertension, antihypertensive drugs, and mortality from cancer among women. J Hypertens 1998, 16:941–947.PubMedCrossRefGoogle Scholar
  14. 14.
    Rosenberg L, Rao RS, Palmer JR, et al.: Calcium channel blockers and the risk of cancer. JAMA 1998, 279:1000–1004.PubMedCrossRefGoogle Scholar
  15. 15.
    Reserpine and breast cancer. Lancet 1974, 2:669–671.Google Scholar
  16. 16.
    Mellemgaard A, Moller H, Olsen JH: Diuretics may increase risk of renal cell carcinoma. Cancer Causes Control 1992, 3:309–312.PubMedCrossRefGoogle Scholar
  17. 17.
    Kreiger N, Marrett LD, Dodds L, et al.: Risk factors for renal cell carcinoma: results of a population-based case-control study. Cancer Causes Control 1993, 4:101–110.PubMedCrossRefGoogle Scholar
  18. 18.
    Mellemgaard A, Niwa S, Mehl ES, et al.: Risk factors for renal cell carcinoma in Denmark: role of medication and medical history. Int J Epidemiol 1994, 23:923–930.PubMedCrossRefGoogle Scholar
  19. 19.
    Finkle WD, McLaughlin JK, Rasgon SA, et al.: Increased risk of renal cell cancer among women using diuretics in the United States. Cancer Causes Control 1993, 4:555–558.PubMedCrossRefGoogle Scholar
  20. 20.
    Hiatt RA, Tolan K, Quesenberry CP Jr: Renal cell carcinoma and thiazide use: a historical, case-control study (California, USA). Cancer Causes Control 1994, 5:319–325.PubMedCrossRefGoogle Scholar
  21. 21.
    Weinmann S, Glass AG, Weiss NS, et al.: Use of diuretics and other antihypertensive medications in relation to the risk of renal cell cancer. Am J Epidemiol 1994, 140:792–804.PubMedGoogle Scholar
  22. 22.
    Pahor M, Guralnik JM, Salive ME, et al.: Do calcium channel blockers increase the risk of cancer? Am J Hypertens 1996, 9:695–699.PubMedCrossRefGoogle Scholar
  23. 23.
    Pahor M, Guralnik JM, Ferrucci L, et al.: Calcium-channel blockade and incidence of cancer in aged populations. Lancet 1996, 348:493–497.PubMedCrossRefGoogle Scholar
  24. 24.
    Fitzpatrick AL, Daling JR, Furberg CD, et al.: Use of calcium channel blockers and breast carcinoma risk in postmenopausal women. Cancer 1997, 80:1438–1447.PubMedCrossRefGoogle Scholar
  25. 25.
    Dyer AR, Stamler J, Berkson DM, et al.: High blood-pressure: a risk factor for cancer mortality? Lancet 1975, 1:1051–1056.PubMedCrossRefGoogle Scholar
  26. 26.
    Grossman E, Messerli FH, Goldbourt U: Antihypertensive therapy and the risk of malignancies. Eur Heart J 2001, 22:1343–1352.PubMedCrossRefGoogle Scholar
  27. 27.
    McCredie M, Stewart JH: Risk factors for kidney cancer in New South Wales, Australia. II. Urologic disease, hypertension, obesity, and hormonal factors. Cancer Causes Control 1992, 3:323–331.PubMedCrossRefGoogle Scholar
  28. 28.
    Andersson OK, Almgren T, Persson B, et al.: Survival in treated hypertension: follow up study after two decades. BMJ 1998, 317:167–1671.PubMedGoogle Scholar
  29. 29.
    Armstrong B, Stevens N, Doll R: Retrospective study of the association between use of rauwolfia derivatives and breast cancer in English women. Lancet 1974, 2:672–675.PubMedCrossRefGoogle Scholar
  30. 30.
    Heinonen OP, Shapiro S, Tuominen L, Turunen MI: Reserpine use in relation to breast cancer. Lancet 1974, 2:675–677.PubMedCrossRefGoogle Scholar
  31. 31.
    Armstrong B, Skegg D, White G, Doll R: Rauwolfia derivatives and breast cancer in hypertensive women. Lancet 1976, 2:8–12.PubMedCrossRefGoogle Scholar
  32. 32.
    Kodlin D, McCarthy N: Reserpine and breast cancer. Cancer 1978, 41:761–768.PubMedCrossRefGoogle Scholar
  33. 33.
    Labarthe DR, O’Fallon WM: Reserpine and breast cancer. A community-based longitudinal study of 2,000 hypertensive women. JAMA 1980, 243:2304–2310.PubMedCrossRefGoogle Scholar
  34. 34.
    Curb JD, Hardy RJ, Labarthe DR, et al.: Reserpine and breast cancer in the Hypertension Detection and Follow-Up Program. Hypertension 1982, 4:307–311.PubMedGoogle Scholar
  35. 35.
    Friedman GD: Rauwolfia and breast cancer: no relation found in long term users age fifty and over. J Chron Dis 1983, 36:367–370.PubMedCrossRefGoogle Scholar
  36. 36.
    Newball HH, Byar DP: Does reserpine increase prolactin and exacerbate cancer of prostate? Case control study. Urology 1973, 2:525–529.PubMedCrossRefGoogle Scholar
  37. 37.
    Byar DP, Blackard CE: Letters: reserpine and prostatic cancer. Urology 1975, 5:158–159.PubMedCrossRefGoogle Scholar
  38. 38.
    Yu MC, Mack TM, Hanisch R, et al.: Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. J Natl Cancer Inst 1986, 77:351–356.PubMedGoogle Scholar
  39. 39.
    Shapiro JA, Williams MA, Weiss NS, et al.: Hypertension, antihypertensive medication use, and risk of renal cell carcinoma. Am J Epidemiol 1999, 149:521–530.PubMedGoogle Scholar
  40. 40.
    Prineas RJ, Folsom AR, Zhang ZM, et al.: Nutrition and other risk factors for renal cell carcinoma in postmenopausal women. Epidemiology 1997, 8:31–36.PubMedCrossRefGoogle Scholar
  41. 41.
    Heath CW Jr, Lally CA, Calle EE, et al.: Hypertension, diuretics, and antihypertensive medications as possible risk factors for renal cell cancer. Am J Epidemiol 1997, 145:607–613.PubMedGoogle Scholar
  42. 42.
    Lijinsky W, Reuber MD: Pathologic effects of chronic administration of hydrochlorothiazide, with and without sodium nitrite, to F344 rats. Toxicol Ind Health 1987, 3:413–422.PubMedGoogle Scholar
  43. 43.
    Loffing J, Loffing-Cueni D, Hegyi I, et al.: Thiazide treatment of rats provokes apoptosis in distal tubule cells. Kidney Int 1996, 50:1180–1190.PubMedCrossRefGoogle Scholar
  44. 44.
    Tenenbaum A, Grossman E, Fisman EZ, et al.: Long-term diuretic therapy in patients with coronary disease: increased colon cancer-related mortality over a 5-year follow-up. J Hum Hypertens 2001, 15:373–379. Long-term exposure to diuretic therapy is associated with an increased risk for colon cancer.PubMedCrossRefGoogle Scholar
  45. 45.
    Tenenbaum A, Motro M, Jonas M, et al.: Is diuretic therapy associated with an increased risk of colon cancer? Am J Med 2001, 110:143–145.PubMedCrossRefGoogle Scholar
  46. 46.
    Lilienfeld AM, Chang L, Thomas DB, Levin ML: Rauwolfia derivatives and breast cancer. Johns Hopkins Med J 1976, 139:41–50.PubMedGoogle Scholar
  47. 47.
    Aromaa A, Hakama M, Hakulinen T, et al.: Breast cancer and use of rauwolfia and other antihypertensive agents in hypertensive patients: a nationwide case-control study in Finland. Int J Cancer 1976, 18:727–738.PubMedCrossRefGoogle Scholar
  48. 48.
    Lindholm LH, Anderson H, Ekbom T, et al.: Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial. Lancet 2001, 358:539–544.PubMedCrossRefGoogle Scholar
  49. 49.
    Coope J, Warrender TS: Randomised trial of treatment of hypertension in elderly patients in primary care. BMJ (Clin Res Ed) 1986, 293:1145–1151.Google Scholar
  50. 50.
    UK Prospective Diabetes Study Group: Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998, 317:713–720.Google Scholar
  51. 51.
    Zavanella T, Radaelli G, Girotti P, et al.: Evaluation of the tumor-promoting activity of two beta-adrenoreceptor blocking agents, propranolol and atenolol, in liver of Fischer 344 rats. Carcinogenesis 1994, 15:2531–2539.PubMedCrossRefGoogle Scholar
  52. 52.
    Ioannides C, Okine L, Parke DV: Effects of beta-adrenoceptor antagonists on the hepatic mixed-function oxygenases in the rat. Br J Pharmacol 1979, 67:451P-452P.PubMedGoogle Scholar
  53. 53.
    Boyd H, Martin TJ: The effect of propranolol on induction of rat liver tumors by a chemical carcinogen. Mol Pharmacol 1977, 13:576–578.PubMedGoogle Scholar
  54. 54.
    Gurkalo VK, Zabezhinski MA: On participation of the autonomic nervous system in the mechanisms of chemical carcinogenesis. Neoplasma 1982, 29:301–307.PubMedGoogle Scholar
  55. 55.
    Hole DJ, Hawthorne VM, Isles CG, et al.: Incidence of and mortality from cancer in hypertensive patients. BMJ 1993, 306:609–611.PubMedGoogle Scholar
  56. 56.
    Fletcher AE, Beevers DG, Bulpitt CJ, et al.: Cancer mortality and atenolol treatment. BMJ 1993, 306:622–623.PubMedGoogle Scholar
  57. 57.
    Jick H, Jick S, Derby LE, et al.: Calcium-channel blockers and risk of cancer. Lancet 1997, 349:525–528.PubMedCrossRefGoogle Scholar
  58. 58.
    Messerli FH, Grossman E: Antihypertensive agents and the risk of cancer. JAMA 1998, 280:600.PubMedCrossRefGoogle Scholar
  59. 59.
    Mickisch GH, Kossig J, Keilhauer G, et al.: Effects of calcium antagonists in multidrug resistant primary human renal cell carcinomas. Cancer Res 1990, 50:3670–3674.PubMedGoogle Scholar
  60. 60.
    al-Shabanah OA, Osman AM, al-Harbi MM, et al.: Diltiazem potentiation of doxorubicin cytotoxicity and cellular uptake in Ehrlich ascites carcinoma cells. Chemotherapy 1995, 41:368–377.PubMedCrossRefGoogle Scholar
  61. 61.
    al-Gharably NM, Osman AM, al-Shabanah OA, et al.: Potentiation of doxorubicin cytotoxicity by the calcium channel blocker verapamil in Ehrlich ascites cells. Chemotherapy 1993, 39:410–415.PubMedCrossRefGoogle Scholar
  62. 62.
    Kunert-Radek J, Stepien H, Radek A, et al.: Inhibitory effect of calcium channel blockers on proliferation of human glioma cells in vitro. Acta Neurol Scand 1989, 79:166–169.PubMedCrossRefGoogle Scholar
  63. 63.
    Lee YS, Sayeed MM, Wurster RD: Intracellular Ca2+ mediates the cytotoxicity induced by bepridil and benzamil in human brain tumor cells. Cancer Lett 1995, 88:87–91.PubMedCrossRefGoogle Scholar
  64. 64.
    Raderer M, Scheithauer W: Clinical trials of agents that reverse multidrug resistance. A literature review. Cancer 1993, 72:3553–3563.PubMedCrossRefGoogle Scholar
  65. 65.
    Taylor JM, Simpson RU: Inhibition of cancer cell growth by calcium channel antagonists in the athymic mouse. Cancer Res 1992, 52:2413–2418.PubMedGoogle Scholar
  66. 66.
    Rasmussen H, Barrett PQ: Calcium messenger system: an integrated view. Physiol Rev 1984, 64:938–984.PubMedGoogle Scholar
  67. 67.
    Lichtlen PR, Hugenholtz PG, Rafflenbeul W, et al.: Retardation of angiographic progression of coronary artery disease by nifedipine. Results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). Lancet 1990, 335:1109–1113.PubMedCrossRefGoogle Scholar
  68. 68.
    Jonas M, Goldbourt U, Boyko V, et al.: Nifedipine and cancer mortality: ten-year follow-up of 2607 patients after acute myocardial infarction. Cardiovasc Drugs Ther 1998, 12:177–181.PubMedCrossRefGoogle Scholar
  69. 69.
    Hole DJ, Gillis CR, McCallum IR, et al.: Cancer risk of hypertensive patients taking calcium antagonists. J Hypertens 1998, 16:119–124.PubMedCrossRefGoogle Scholar
  70. 70.
    Borhani NO, Mercuri M, Borhani PA, et al.: Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial. JAMA 1996, 276:785–791.PubMedCrossRefGoogle Scholar
  71. 71.
    Packer M, O’Connor CM, Ghali JK, et al., for the Prospective Randomized Amlodipine Survival Evaluation Study Group (PRAISE): Effect of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med 1996, 335:1107–1114.PubMedCrossRefGoogle Scholar
  72. 72.
    Gong L, Zhang W, Zhu Y, et al., with 11 collaborating centres in the Shangai area: Shanghai trial of nifedipine in the elderly (STONE). J Hypertens 1996, 14:1237–1245.PubMedCrossRefGoogle Scholar
  73. 73.
    Liu L, Wang JG, Gong L, et al.: Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (Syst-China) Collaborative Group. J Hypertens 1998, 16(12 Pt 1):1823–1829.PubMedCrossRefGoogle Scholar
  74. 74.
    Staessen JA, Fagard R, Thijs L, et al.: Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997, 350:757–764.PubMedCrossRefGoogle Scholar
  75. 75.
    Braun S, Boyko V, Behar S, et al.: Calcium channel blocking agents and risk of cancer in patients with coronary heart disease. Benzafibrate Infarction Prevention (BIP) study research group. J Am Coll Cardiol 1998, 31:804–808.PubMedCrossRefGoogle Scholar
  76. 76.
    Olsen JH, Toft Sorensen HT, Friis S, et al.: Cancer risk in users of calcium channel blockers. Hypertension 1997, 29:1091–1094.PubMedGoogle Scholar
  77. 77.
    Brandenburg NA, Backstrom JT, Hinkle RL: Calcium channel blockers and cancer: the evidence against an association [letter]. Am J Hypertens 1996, 9(10Pt1V):1049–1050.PubMedCrossRefGoogle Scholar
  78. 78.
    Stahl M, Bulpitt CJ, Palmer AJ, et al.: Calcium channel blockers, ACE inhibitors, and the risk of cancer in hypertensive patients: a report from the Department of Health Hypertension Care Computing Project (DHCCP). J Hum Hypertens 2000, 14:299–304.PubMedCrossRefGoogle Scholar
  79. 79.
    Meier CR, Derby LE, Jick SS, Jick H: Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Arch Intern Med 2000, 160:349–353.PubMedCrossRefGoogle Scholar
  80. 80.
    Vezina RM, Lesko SM, Rosenberg L, Shapiro S: Calcium channel blocker use and the risk of prostate cancer. Am J Hypertens 1998, 11:1420–1425.PubMedCrossRefGoogle Scholar
  81. 81.
    Sorensen HT, Olsen JH, Mellemkjaer L, et al.: Cancer risk and mortality in users of calcium channel blockers. A cohort study. Cancer 2000, 89:165–170. Data from this study make it unlikely that calcium antagonists increase the risk of malignancy.PubMedCrossRefGoogle Scholar
  82. 82.
    Cohen HJ, Pieper CF, Hanlon JT, et al.: Calcium channel blockers and cancer. Am J Med 2000, 108:210–215.PubMedCrossRefGoogle Scholar
  83. 83.
    Michels KB, Rosner BA, Walker AM, et al.: Calcium channel blockers, cancer incidence, and cancer mortality in a cohort of U.S. women: the nurses’ health study. Cancer 1998, 83:2003–2007.PubMedCrossRefGoogle Scholar
  84. 84.
    Kanamasa K, Kimura A, Miyataka M, et al.: Incidence of cancer in postmyocardial infarction patients treated with short-acting nifedipine and diltiazem. Secondary Prevention Group. Cancer 1999, 85:1369–1374.PubMedCrossRefGoogle Scholar
  85. 85.
    Sajadieh A, Storm HH, Hansen JF: Verapamil and risk of cancer in patients with coronary artery disease. DAVIT Study Group. Danish Verapamil Infarction Trial. Am J Cardiol 1999, 83:1419–1422.PubMedCrossRefGoogle Scholar
  86. 86.
    Reddy MK, Baskaran K, Molteni A: Inhibitors of angiotensinconverting enzyme modulate mitosis and gene expression in pancreatic cancer cells. Proc Soc Exp Biol Med 1995, 210:221–226.PubMedGoogle Scholar
  87. 87.
    Small W Jr, Molteni A, Kim YT, et al.: Captopril modulates hormone receptor concentration and inhibits proliferation of human mammary ductal carcinoma cells in culture. Breast Cancer Res Treat 1997, 44:217–224.PubMedCrossRefGoogle Scholar
  88. 88.
    Chen L, Re RN, Prakash O, Mondal D: Angiotensin-converting enzyme inhibition reduces neuroblastoma cell growth rate. Proc Soc Exp Biol Med 1991, 196:280–283.PubMedGoogle Scholar
  89. 89.
    Ward WF, Molteni A, Ts’ao C, Hinz JM: The effect of Captopril on benign and malignant reactions in irradiated rat skin. Br J Radiol 1990, 63:349–354.PubMedCrossRefGoogle Scholar
  90. 90.
    Ward WF, Molteni A, Kim YT, et al.: captopril inhibits mitosis and growth of diethylnitrosamine-induced preneoplastic hepatic foci in F344 rats [abstract]. FASEB J 1992, 5:6.Google Scholar
  91. 91.
    Bastiaens MT, Zwan NV, Verschueren GL, et al.: Three cases of pemphigus vegetans: induction by enalapril--association with internal malignancy. Int J Dermatol 1994, 33:168–171.PubMedGoogle Scholar
  92. 92.
    Larbre JP, Nicolas JF, Collet P, et al.: Kaposi’s sarcoma in a patient with rheumatoid arthritis possible responsibility of captopril in the development of lesions. J Rheumatol 1991, 18:476–477.PubMedGoogle Scholar
  93. 93.
    Furness PN, Goodfield MJ, MacLennan KA, et al.: Severe cutaneous reactions to captopril and enalapril, histological study and comparison with early mycosis fungoides. J Clin Pathol 1986, 39:902–907.PubMedGoogle Scholar
  94. 94.
    Puppin D Jr, Rybojad M, de la Chapelle C, Morel P: Kaposi’s sarcoma associated with captopril [letter]. Lancet 1990, 336:1251–1252.PubMedCrossRefGoogle Scholar
  95. 95.
    Carroll J, Thaler M, Grossman E, et al.: Generalized pustular eruption associated with converting enzyme inhibitor therapy. Cutis 1995, 56:276–278.PubMedGoogle Scholar
  96. 96.
    Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991, 325:293–302.Google Scholar
  97. 97.
    Maschio G, Alberti D, Janin G, et al.: Effect of the angiotensinconverting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996, 334:939–945.PubMedCrossRefGoogle Scholar
  98. 98.
    Lever AF, Hole DJ, Gillis CR, et al.: Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet 1998, 352:179–184. Long-term use of ACE inhibitors seemed to exert a protective effect against malignancy.PubMedCrossRefGoogle Scholar
  99. 99.
    Weisenburger DD: Immunoblastic lymphadenopathy associated with methyldopa therapy: a case report. Cancer 1978, 42:2322–2327.PubMedCrossRefGoogle Scholar
  100. 100.
    Broden G, Bengtsson L: Biliary carcinoma associated with methyldopa therapy. Acta Chir Scand Suppl 1980, 500:7–12.PubMedGoogle Scholar
  101. 101.
    Strom BL, Hibberd PL, Stolley PD: No evidence of association between methyldopa and biliary carcinoma. Int J Epidemiol 1985, 14:86–90.PubMedCrossRefGoogle Scholar
  102. 102.
    Kaufman DW, Kelly JP, Rosenberg L, et al.: Hydralazine and breast cancer. J Natl Cancer Inst 1987, 78:243–246.PubMedGoogle Scholar
  103. 103.
    Kaufman DW, Kelly JP, Rosenberg L, et al.: Hydralazine use in relation to cancers of the lung, colon, and rectum. Eur J Clin Pharmacol 1989, 36:259–264.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2002

Authors and Affiliations

  • Ehud Grossman
  • Franz H. Messerli
    • 1
  • Uri Goldbourt
  1. 1.Ochsner Clinic FoundationNew OrleansUSA

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