Epidemiology and Risk Factors

Abstract

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

D. Baris^1,+, G. Gridley¹, E. Ron¹, E. Weiderpass², L. Mellemkjaer³, A. Ekbom², J.H. Olsen³, J.A. Baron⁴, J.F. Fraumeni, Jr¹

¹National Cancer Institute, Bethesda, Maryland, USA; ⁺Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 8122, Bethesda, MD, USA 20892-7240. Ph.: (301) 435-4707; Fax: (301) 402-1891; Email: barisd@mail.nih.gov; ²Karolinska Institute, Stockholm, Sweden and International Agency for Research on Cancer, Lyon, France; ³Danish Cancer Society, Copenhagen, Denmark; ⁴,Dartmouth Medical School, Hanover, New Hampshire, USA.

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.

Keywords: acromegaly, cancer, cohort

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