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Cancer Causes & Control

, Volume 13, Issue 5, pp 395–400 | Cite as

Acromegaly and cancer risk: a cohort study in Sweden and Denmark

  • D. Baris
  • G. Gridley
  • E. Ron
  • E. Weiderpass
  • L. Mellemkjaer
  • A. Ekbom
  • J.H. Olsen
  • J.A. Baron
  • J.F. FraumeniJr
Article

Abstract

Objective: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark. Methods: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977–1993; Sweden 1965–1993) were linked to tumor registry data for up to 15–28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly. Results: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5, 95% CI = 1.3–1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.6–2.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2–17.4), colon (SIR = 2.6, 95% CI = 1.6–3.8), and rectum (SIR = 2.5, 95% CI = 1.3–4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI = 1.2–5.0), thyroid (SIR = 3.7, 95% CI = 1.8–10.9), kidney (SIR = 3.2, 95% CI = 1.6–5.5), and bone (SIR = 13.8, 95% CI = 1.7–50.0). Conclusions: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-1 system in the etiology of various cancers.

acromegaly cancer cohort 

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References

  1. 1.
    Melmed S (1990) Acromegaly. N Engl J Med 322: 966-977.Google Scholar
  2. 2.
    Delhougne B, Deneux C, Abs R, et al. (1995) The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients. J Clin Endocrinol Metab 80: 3223-3226.Google Scholar
  3. 3.
    Terzolo M, Tappero G, Borretta G, et al. (1994) High prevalence of colonic polyps in patients with acromegaly. Influence of sex and age. Arch Intern Med 154: 1272-1276.Google Scholar
  4. 4.
    Brunner JE, Johnson CC, Zafar S, Peterson EL, Brunner JF, Mellinger RC (1990) Colon cancer and polyps in acromegaly: increased risk associated with family history of colon cancer. Clin Endocrinol (Oxf) 32: 65-71.Google Scholar
  5. 5.
    Ezzat S, Melmed S (1991) Clinical review 18: Are patients with acromegaly at increased risk for neoplasia? J Clin Endocrinol Metab 72: 245-249.Google Scholar
  6. 6.
    Orme SM, McNally RJ, Cartwright RA, Belchetz PE (1998) Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 83: 2730-2734.Google Scholar
  7. 7.
    Pines A, Rozen P, Ron E, Gilat T (1985) Gastrointestinal tumors in acromegalic patients. Am J Gastroenterol 80: 266-269.Google Scholar
  8. 8.
    Popovic V, Damjanovic S, Micic D, et al. (1998) Increased incidence of neoplasia in patients with pituitary adenomas. The Pituitary Study Group. Clin Endocrinol (Oxf) 49: 441-445.Google Scholar
  9. 9.
    Ron E, Gridley G, Hrubec Z, Page W, Arora S, Fraumeni JF, Jr (1991) Acromegaly and gastrointestinal cancer. Cancer 68: 1673-1677.Google Scholar
  10. 10.
    Jenkins PJ, Besser M (2001) Clinical perspective: acromegaly and cancer: a problem. J Clin Endocrinol Metab 86: 2935-2941.Google Scholar
  11. 11.
    Manousos O, Souglakos J, Bosetti C, et al. (1999) IGF-I and IGFII in relation to colorectal cancer. Int J Cancer 83: 15-17.Google Scholar
  12. 12.
    Ma J, Pollak MN, Giovannucci E, et al. (1999) Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 91: 620-625.Google Scholar
  13. 13.
    Giovannucci E, Pollak MN, Platz EA, et al. (2000) A prospective study of plasma insulin-like growth factor-1 and binding protein-3 Acromegaly and risk of cancer 399 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomarkers Prev 9: 345-349.Google Scholar
  14. 14.
    Chan JM, Stampfer MJ, Giovannucci E, et al. (1998) Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279: 563-566.Google Scholar
  15. 15.
    Bohlke K, Cramer DW, Trichopoulos D, Mantzoros CS (1998) Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology 9: 570-573.Google Scholar
  16. 16.
    Linet MS, Gridley G, Nyren O, et al. (1999) Primary liver cancer, other malignancies, and mortality risks following porphyria: a cohort study in Denmark and Sweden. Am J Epidemiol 149: 1010-1015.Google Scholar
  17. 17.
    Breslow NE, Day NE (1987) Statistical methods in cancer research. Vol. II: The design and analysis of cohort studies. Lyon: International Agency for Research on Cancer.Google Scholar
  18. 18.
    Brada M, Ford D, Ashley S, et al. (1992) Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. BMJ 304: 1343-1346.Google Scholar
  19. 19.
    Balkany C, Cushing GW (1995) An association between acromegaly and thyroid carcinoma. Thyroid 5: 47-50.Google Scholar
  20. 20.
    Cheung NW, Boyages SC (1997) Increased incidence of neoplasia in females with acromegaly. Clin Endocrinol (Oxf) 47: 323-327.Google Scholar
  21. 21.
    Burroughs KD, Dunn SE, Barrett JC, Taylor JA (1999) Insulinlike growth factor-I: a key regulator of human cancer risk? J Natl Cancer Inst 91: 579-581.Google Scholar
  22. 22.
    Cats A, Dullaart RP, Kleibeuker JH, et al. (1996) Increased epithelial cell proliferation in the colon of patients with acromegaly. Cancer Res 56: 523-526.Google Scholar
  23. 23.
    Zhuang Z, Ezzat SZ, Vortmeyer AO, et al. (1997) Mutations of the MEN1 tumor suppressor gene in pituitary tumors. Cancer Res 57: 5446-5451.Google Scholar
  24. 24.
    Barkan AL, Shenker Y, Grekin RJ, Vale WW (1988) Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor: successful treatment with long-acting somatostatin analogue SMS 201-995. Cancer 61: 221-226.Google Scholar
  25. 25.
    Kasagi K, Shimatsu A, Miyamoto S, Misaki T, Sakahara H, Konishi J (1999) Goiter associated with acromegaly: sonographic and scintigraphic findings of the thyroid gland. Thyroid 9: 791-796.Google Scholar
  26. 26.
    Wuster C, Steger G, Schmelzle A, Gottswinter J, Minne HW, Ziegler R (1991) Increased incidence of euthyroid and hyperthyroid goiters independently of thyrotropin in patients with acromegaly. Horm Metab Res 23: 131-134.Google Scholar
  27. 27.
    From G, Mellemgaard A, Knudsen N, Jorgensen T, Perrild H (2000) Review of thyroid cancer cases among patients with previous benign thyroid disorders. Thyroid 10: 697-700.Google Scholar
  28. 28.
    Franceschi S, Preston-Martin S, Dal Maso L, et al. (1999) A pooled analysis of case-control studies of thyroid cancer. IV. Benign thyroid diseases. Cancer Causes Control 10: 583-595.Google Scholar
  29. 29.
    Tramontano D, Cushing GW, Moses AC, Ingbar SH(1986) Insulin-like growth factor-I stimulates the growth of rat thyroid cells in culture and synergizes the stimulation of DNA synthesis induced by TSHand Graves'-IgG. Endocrinology 119: 940-942.Google Scholar
  30. 30.
    Stratakis CA (2001) Clinical genetics of multiple endocrine neoplasias, Carney complex and related syndromes. J Endocrinol Invest 24: 370-383.Google Scholar
  31. 31.
    Ron E, Saftlas AF (1996) Head and neck radiation carcinogenesis: epidemiologic evidence. Otolaryngol Head Neck Surg 115: 403-408.Google Scholar
  32. 32.
    Tsang RW, Laperriere NJ, Simpson WJ, Brierley J, Panzarella T, Smyth HS (1993) Glioma arising after radiation therapy for pituitary adenoma. A report of four patients and estimation of risk. Cancer 72: 2227-2233.Google Scholar
  33. 33.
    Preston-Martin S, Mack WJ (1996) Neoplasms of the nervous system. In: Schottenfeld D, Fraumeni J.F. Jr, eds. Cancer Epidemiology and Prevention. New York: Oxford University Press, pp. 1231-1281.Google Scholar
  34. 34.
    Ron E, Modan B, Boice JD, Jr, et al. (1988) Tumors of the brain and nervous system after radiotherapy in childhood. N Engl J Med 319: 1033-1039.Google Scholar
  35. 35.
    Cannavo S, Curto L, Fazio R, et al. (1993) Coexistence of growth hormone-secreting pituitary adenoma and intracranial meningioma: a case report and review of the literature. J Endocrinol Invest 16: 703-708.Google Scholar
  36. 36.
    Kellerer M, von Eye CH, Muhlhofer A, et al. (1995) Insulin-and insulin-like growth-factor-I receptor tyrosine-kinase activities in human renal carcinoma. Int J Cancer 62: 501-507.Google Scholar
  37. 37.
    McGuffin WL, Jr., Sherman BM, Roth F, et al. (1974) Acromegaly and cardiovascular disorders. A prospective study. Ann Intern Med 81: 11-18.Google Scholar
  38. 38.
    Yuan JM, Castelao JE, Gago-Dominguez M, Ross RK, Yu MC (1998) Hypertension, obesity and their medications in relation to renal cell carcinoma. Br J Cancer 77: 1508-1513.Google Scholar
  39. 39.
    Chow WH, Gridley G, Fraumeni JF, Jr, Jarvholm B (2000) Obesity, hypertension, and the risk of kidney cancer in men. N Engl J Med 343: 1305-1311.Google Scholar
  40. 40.
    Ratner RE, Hare JW (1983) Association of acromegaly and chondrosarcoma. South Med J 76: 1181-1182.Google Scholar
  41. 41.
    James RA, Dymock RB (1976) Osteosarcoma associated with acromegaly: a case report. Pathology 8: 157-159.Google Scholar
  42. 42.
    Scheven BA, Hamilton NJ, Fakkeldij TM, Duursma SA (1991) Effects of recombinant human insulin-like growth factor I and II (IGF-I/-II) and growth hormone (GH) on the growth of normal adult human osteoblast-like cells and human osteogenic sarcoma cells. Growth Regul 1: 160-167.Google Scholar
  43. 43.
    Mortensen A, Bojsen-Moller M, Rasmussen P (1989) Fibrous dysplasia of the skull with acromegaly and sarcomatous transformation: two cases with a review of the literature. J Neurooncol 7: 25-29.Google Scholar
  44. 44.
    Nabarro JD (1987) Acromegaly. Clin Endocrinol (Oxf) 26: 481-512.Google Scholar
  45. 45.
    Hankinson SE, Willett WC, Colditz GA, et al. (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351: 1393-1396.Google Scholar
  46. 46.
    Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami HO (1997) Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer 76: 1115-1118.Google Scholar
  47. 47.
    Wolk A, Mantzoros CS, Andersson SO, et al. (1998) Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. J Natl Cancer Inst 90: 911-915.Google Scholar
  48. 48.
    Wu X, Yu H, Amos CI, Hong WK, Spitz MR (2000) Joint effect of insulin-like growth factors and mutagen sensitivity in lung cancer risk. J Natl Cancer Inst 92: 737-743.Google Scholar
  49. 49.
    Lukanova A, Toniolo P, Akhmedkhanov A, et al. (2001) A prospective study of insulin-like growth factor-I, IGF-binding proteins-1,-2 and-3 and lung cancer risk in women. Int J Cancer 92: 888-892.Google Scholar
  50. 50.
    Hagg E, Asplund K, Holm J (1988) Acromegaly and multiple myeloma. Ann Intern Med 109: 437-438.Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • D. Baris
    • 1
    • 2
  • G. Gridley
    • 1
  • E. Ron
    • 1
  • E. Weiderpass
    • 3
    • 4
  • L. Mellemkjaer
    • 5
  • A. Ekbom
    • 3
    • 4
  • J.H. Olsen
    • 5
  • J.A. Baron
    • 6
  • J.F. FraumeniJr
    • 1
  1. 1.National Cancer InstituteBethesdaUSA
  2. 2.Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaUSA
  3. 3.Karolinska InstituteStockholmSweden
  4. 4.International Agency for Research on CancerLyonFrance
  5. 5.Danish Cancer SocietyCopenhagenDenmark
  6. 6.Dartmouth Medical SchoolHanoverUSA

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