This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cats, A. Articles by de Vries, E. G. E. Search for Related Content PubMed PubMed Citation Articles by Cats, A. Articles by de Vries, E. G. E.

Increased Epithelial Cell Proliferation in the Colon of Patients with Acromegaly¹

Divisions of Medical Oncology [A. C., E. G. E. d. V.], Endocrinology [R. P. F. D., W. J. S.], and Gastroenterology [A. C., J. H. K.], Department of Internal Medicine, and Departments of Pediatrics [F. K.] and Pathology [M. J. H.], University Hospital, P.O. Box 30.001, 9700 RB Groningen, the Netherlands

To gain insight into the possible physiological mechanisms responsible for the increased incidence of colonic neoplasms in patients with acromegaly, a prospective cohort study was carried out in 30 patients with acromegaly. Seven patients had a newly diagnosed acromegaly and 23 were studied during follow-up. Serum growth hormone and insulin-like growth factor-1 (IGF-1) were determined on two separate occasions. During diagnostic endoscopy, mucosal biopsies were obtained for immunohistochemical determination of sigmoidal epithelial cell proliferation, expressed as labeling index (LI). Duodenal and fecal bile acid analyses were performed using gas-liquid chromatography. Results were compared with normal ranges of the laboratory.

An increased overall LI was found in 54% of the patients. Increased LI of the luminal, middle, and basal crypt compartments was found in 11, 64, and 28%, respectively. Similarly, comparisons of the mean ± SEM of the overall LI and the LI of the middle and basal compartments between acromegalic patients and a control group showed overall LI 10.0 ± 0.8% versus 5.7 ± 0.6% (P < 0.001), middle LI 12.1 ± 1.2% versus 5.0 ± 0.6% (P < 0.001), and basal LI 17.1 ± 1.3% versus 10.8 ± 1.3% (P < 0.01). Duodenal and fecal bile acid proportions were within the normal ranges of the laboratory. There was a positive correlation between growth hormone and overall LI (r = 0.60, P < 0.001) and between IGF-1 and total LI (r = 0.55, P < 0.01) by least square regression analysis. There was no correlation between duodenal bile acid composition and hormone levels. The proportion of secondary bile acids in feces correlated with growth hormone (r = 0.55, P < 0.05) as well as with IGF-1 (r = 0.59, P < 0.05). With multiple regression analyses, only a relation between overall LI and IGF-1 (P = 0.007) remained to hold true. Increased epithelial cell proliferation, most probably due to a direct stimulatory effect of especially IGF-1, contributes to the increased risk of colonic neoplasms in acromegaly.

¹ This study was supported by Grant GUKC 89-08 of the Dutch Cancer Society.

² To whom requests for reprints should be addressed. Phone: +31-50-3616161; Fax: +31-50-3696781.

Received 6/16/95. Accepted 11/28/95.

This article has been cited by other articles:

				J. Sung, Y.-M. Song, D. A. Lawlor, G. D. Smith, and S. Ebrahim Height and Site-specific Cancer Risk: A Cohort Study of a Korean Adult Population Am. J. Epidemiol., July 1, 2009; 170(1): 53 - 64. [Abstract] [Full Text] [PDF]

				S. Melmed Acromegaly N. Engl. J. Med., December 14, 2006; 355(24): 2558 - 2573. [Full Text] [PDF]

				T. O. Keku, P. K. Lund, J. Galanko, J. G. Simmons, J. T. Woosley, and R. S. Sandler Insulin Resistance, Apoptosis, and Colorectal Adenoma Risk Cancer Epidemiol. Biomarkers Prev., September 1, 2005; 14(9): 2076 - 2081. [Abstract] [Full Text] [PDF]

				D. W. Voskuil, A. Vrieling, L. J. van't Veer, E. Kampman, and M. A. Rookus The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary Intervention Strategies Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 195 - 203. [Abstract] [Full Text] [PDF]

				M. Terzolo, G. Reimondo, M. Gasperi, R. Cozzi, R. Pivonello, G. Vitale, A. Scillitani, R. Attanasio, E. Cecconi, F. Daffara, et al. Colonoscopic Screening and Follow-Up in Patients with Acromegaly: A Multicenter Study in Italy J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 84 - 90. [Abstract] [Full Text] [PDF]

				A. Colao, D. Ferone, P. Marzullo, and G. Lombardi Systemic Complications of Acromegaly: Epidemiology, Pathogenesis, and Management Endocr. Rev., February 1, 2004; 25(1): 102 - 152. [Abstract] [Full Text] [PDF]

				Y.-M. Song, G. D. Smith, and J. Sung Adult Height and Cause-specific Mortality: A Large Prospective Study of South Korean Men Am. J. Epidemiol., September 1, 2003; 158(5): 479 - 485. [Abstract] [Full Text] [PDF]

				D. Komninou, A. Ayonote, J. P. Richie Jr., and B. Rigas Insulin Resistance and Its Contribution to Colon Carcinogenesis Experimental Biology and Medicine, April 1, 2003; 228(4): 396 - 405. [Abstract] [Full Text] [PDF]

				P J Jenkins and P D Fairclough Screening guidelines for colorectal cancer and polyps in patients with acromegaly Gut, October 1, 2002; 51(90005): v13 - 14. [Full Text] [PDF]

				M. S. Sandhu, D. B. Dunger, and E. L. Giovannucci Insulin, Insulin-Like Growth Factor-I (IGF-I), IGF Binding Proteins, Their Biologic Interactions, and Colorectal Cancer J Natl Cancer Inst, July 3, 2002; 94(13): 972 - 980. [Abstract] [Full Text] [PDF]

				R Palmqvist, G Hallmans, S Rinaldi, C Biessy, R Stenling, E Riboli, and R Kaaks Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden Gut, May 1, 2002; 50(5): 642 - 646. [Abstract] [Full Text] [PDF]

				L. Le Marchand, T. Donlon, A. Seifried, R. Kaaks, S. Rinaldi, and L. R. Wilkens Association of a Common Polymorphism in the Human GH1 Gene with Colorectal Neoplasia J Natl Cancer Inst, March 20, 2002; 94(6): 454 - 460. [Abstract] [Full Text] [PDF]

				E. Giovannucci Insulin, Insulin-Like Growth Factors and Colon Cancer: A Review of the Evidence J. Nutr., November 1, 2001; 131(11): 3109S - 3120. [Abstract] [Full Text] [PDF]

				J. Ma, E. Giovannucci, M. Pollak, J. M. Chan, J. M. Gaziano, W. Willett, and M. J. Stampfer Milk Intake, Circulating Levels of Insulin-Like Growth Factor-I, and Risk of Colorectal Cancer in Men J Natl Cancer Inst, September 5, 2001; 93(17): 1330 - 1336. [Abstract] [Full Text] [PDF]

				P. J. Jenkins and M. Besser CLINICAL PERSPECTIVE: Acromegaly and Cancer: A Problem J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 2935 - 2941. [Full Text] [PDF]

				J. Khosravi, A. Diamandi, J. Mistry, and A. Scorilas Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-3 in Benign Prostatic Hyperplasia and Prostate Cancer J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 694 - 699. [Abstract] [Full Text]

				P. J. Jenkins, V. Frajese, A-M. Jones, C. Camacho-Hubner, D. G. Lowe, P. D. Fairclough, S. L. Chew, A. B. Grossman, J. P. Monson, and G. M. Besser Insulin-Like Growth Factor I and the Development of Colorectal Neoplasia in Acromegaly J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3218 - 3221. [Abstract] [Full Text]

				E. Giovannucci, M. N. Pollak, E. A. Platz, W. C. Willett, M. J. Stampfer, N. Majeed, G. A. Colditz, F. E. Speizer, and S. E. Hankinson A Prospective Study of Plasma Insulin-like Growth Factor-1 and Binding Protein-3 and Risk of Colorectal Neoplasia in Women Cancer Epidemiol. Biomarkers Prev., April 1, 2000; 9(4): 345 - 349. [Abstract] [Full Text]

				G. D. Smith, C. Hart, M. Upton, D. Hole, C. Gillis, G. Watt, and V. Hawthorne Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality J Epidemiol Community Health, February 1, 2000; 54(2): 97 - 103. [Abstract] [Full Text]

				P J JENKINS, G M BESSER, and P D FAIRCLOUGH Colorectal neoplasia in acromegaly Gut, May 1, 1999; 44(5): 585 - 587. [Full Text] [PDF]

				J. Ma, M. N. Pollak, E. Giovannucci, J. M. Chan, Y. Tao, C. H. Hennekens, and M. J. Stampfer 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, April 7, 1999; 91(7): 620 - 625. [Abstract] [Full Text] [PDF]