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DOI: 10.1055/s-2004-814150
Acromegaly and Colorectal Cancer: A Comprehensive Review of Epidemiology, Biological Mechanisms, and Clinical Implications
Publikationsverlauf
Received 2 September 2003
Accepted after Revision 1 October 2003
Publikationsdatum:
07. Januar 2004 (online)
![](https://www.thieme-connect.de/media/hmr/20031112/lookinside/thumbnails/10.1055-s-2004-814150-1.jpg)
Abstract
Acromegaly is an endocrine disorder characterised by sustained hypersecretion of growth hormone (GH) with concomitant elevation of insulin-like growth factor (IGF)-I, and is associated with malignancy and premature mortality from cardiovascular and respiratory diseases. In particular, there may be an increased risk of colorectal neoplasia, but the exact extent of this is contentious. Colonoscopy-based studies of adenoma prevalence rates in acromegalic patients are misleading, but population-based studies on colorectal cancer risk are more consistent - a meta-analysis estimated a pooled risk ratio of 2.04 (95 % CI: 1.32, 3.14). Possible mechanisms underlying this increased risk include direct actions as a consequence of elevated levels of circulating GH and IGF-I and/or other perturbations within the IGF system. Other possible mechanisms include altered bile acid secretion, altered cellular immunity, hyperinsulinaemia, shared genetic susceptibility and increased bowel length. However, most explanations only offer indirect evidence, and the expectation of acromegaly as a natural model of colorectal carcinogenesis has not materialised. From a clinical perspective, it seems reasonable to consider a once-only colonoscopic screening at approximately age 55 years, but potential risks and benefits should be balanced.
Key words
Acromegaly - Colorectal cancer - Growth hormone - Insulin-like growth factors - Screening
References
- 1 Duncan E, Wass J A. Investigation protocol: acromegaly and its investigation. Clin Endocrinol Oxf. 1999; 50 285-293
- 2 Melmed S, Vance M L, Barkan A L. et al . Current status and future opportunities for controlling acromegaly. Pituitary. 2002; 5 185-196
- 3 Alexander L, Appleton D, Hall R, Ross W M, Wilkinson R. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol Oxf. 1980; 12 71-79
- 4 Mindermann T, Wilson C B. Age-related and gender-related occurrence of pituitary adenomas. Clin Endocrinol (Oxf). 1994; 41 359-364
- 5 Molitch M E. Clinical manifestations of acromegaly. Endocrinol Metab Clin North Am. 1992; 21 597-614
- 6 Wright A D, Hill D M, Lowy C, Fraser T R. Mortality in acromegaly. Q J Med. 1970; 39 1-16
- 7 Wass J A, Cudworth A G, Bottazzo G F, Woodrow J C, Besser G M. An assessment of glucose intolerance in acromegaly and its response to medical treatment. Clin Endocrinol Oxf. 1980; 12 53-59
- 8 Merola B, Cittadini A, Colao A. et al . Chronic treatment with the somatostatin analog octreotide improves cardiac abnormalities in acromegaly. J Clin Endocrinol Metab. 1993; 77 790-793
- 9 Orme S M, McNally R J, Cartwright R A, Belchetz P E. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab. 1998; 83 2730-2734
- 10 Moon H D, Simpson M E, Li C H, Evans H M. Neoplasms in rats treated with pituitary growth hormone I. Pulmonary and lymphatic tissues. Cancer Res. 1950; 10 297-308
- 11 Pines A, Rozen P, Ron E, Gilat T. Gastrointestinal tumors in acromegalic patients. Am J Gastroenterol. 1985; 80 266-269
- 12 Nabarro J D. Acromegaly. Clin Endocrinol Oxf. 1987; 26 481-512
- 13 Barzilay J, Heatley G J, Cushing G W. Benign and malignant tumors in patients with acromegaly. Arch Intern Med. 1991; 151 1629-1632
- 14 Parkin D M. Global cancer statistics in the year 2000. Lancet Oncol. 2001; 2 533-543
- 15 Muto T, Bussey H J, Morson B C. The evolution of cancer of the colon and rectum. Cancer. 1975; 36 2251-2270
- 16 Renehan A G, O'Dwyer S T, Haboubi N J, Potten C S. Early cellular events in colorectal carcinogenesis. Colorectal Dis. 2002; 4 76-89
- 17 Roncucci L, Pedroni M, Vaccina F, Benatti P, Marzona L, De Pol A. Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics. Cell Prolif. 2000; 33 1-18
- 18 Hamilton S R, Aaltonen L A. WHO (World Health Organisation) Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. Lyon; IARC Press 2000
- 19 Atkin W S, Morson B C, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med. 1992; 326 658-662
- 20 Atkin W S, Saunders B P. Surveillance guidelines after removal of colorectal adenomatous polyps. Gut. 2002; 51(Suppl 5) V6-V9
- 21 Janne P A, Mayer R J. Chemoprevention of colorectal cancer. N Engl J Med. 2000; 342 1960-1968
- 22 Haydon A M, Jass J R. Emerging pathways in colorectal-cancer development. Lancet Oncol. 2002; 3 83-88
- 23 Vogelstein B, Fearon E R, Hamilton S R. et al . Genetic alterations during colorectal-tumor development. N Engl J Med. 1988; 319 525-532
- 24 Fearon E R, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990; 61 759-767
- 25 Wright N A. Epithelial stem cell repertoire in the gut: clues to the origin of cell lineages, proliferative units and cancer. Int J Exp Pathol. 2000; 81 117-143
- 26 Renehan A G, Booth C, Byrne G, Potten C S. The Genetic Regulation of Intestinal Stem Cells and the Origin of Colon Cancer. Br J Cancer (in press). ;
- 27 Klein I, Parveen G, Gavaler J S, Vanthiel D H. Colonic polyps in patients with acromegaly. Ann Intern Med. 1982; 97 27-30
- 28 Ituarte E M, Petrini J, Hershman J M. Acromegaly and colon cancer. Ann Intern Med. 1984; 101 627-628
- 29 Brunner J E, Johnson C C, Zafar S, Peterson E L, Brunner J F, Mellinger R C. Colon cancer and polyps in acromegaly: increased risk associated with family history of colon cancer. Clin Endocrinol Oxf. 1990; 32 65-71
- 30 Ezzat S, Strom C, Melmed S. Colon polyps in acromegaly. Ann Intern Med. 1991; 114 754-755
- 31 Ortego J, Vega B, Sampedro J, Escalada J, Boixeda D, Varela C. Neoplastic colonic polyps in acromegaly. Horm Metab Res. 1994; 26 609-610
- 32 Ladas S D, Thalassinos N C, Ioannides G, Raptis S A. Does acromegaly really predispose to an increased prevalence of gastrointestinal tumours?. Clin Endocrinol Oxf. 1994; 41 597-601
- 33 Vasen H F, van Erpecum K J, Roelfsema F. et al . Increased prevalence of colonic adenomas in patients with acromegaly. Eur J Endocrinol. 1994; 131 235-237
- 34 Terzolo M, Tappero G, Borretta G. et al . High prevalence of colonic polyps in patients with acromegaly. Influence of sex and age. Arch Intern Med. 1994; 154 1272-1276
- 35 Delhougne B, Deneux C, Abs R. et al . The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients. J Clin Endocrinol Metab. 1995; 80 3223-3226
- 36 Colao A, Balzano A, Ferone D. et al . Increased prevalence of colonic polyps and altered lymphocyte subset pattern in the colonic lamina propria in acromegaly. Clin Endocrinol Oxf. 1997; 47 23-28
- 37 Jenkins P J, Fairclough P D, Richards T. et al . Acromegaly, colonic polyps and carcinoma. Clin Endocrinol Oxf. 1997; 47 17-22
- 38 Renehan A G, Bhaskar P, Painter J E. et al . The prevalence and characteristics of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000; 85 3417-3424
- 39 Jenkins P J, Besser G M, Fairclough P D. Colorectal neoplasia in acromegaly. Gut. 1999; 44 585-587
- 40 Lieberman D A, Weiss D G, Bond J H, Ahnen D J, Garewal H, Chejfec G. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med. 2000; 343 162-168
- 41 Imperiale T F, Wagner D R, Lin C Y, Larkin G N, Rogge J D, Ransohoff D F. Risk of advanced proximal neoplasms in asymptomatic adults according to the distal colorectal findings. N Engl J Med. 2000; 343 169-174
- 42 Pinsky P F. A multi-stage model of adenoma development. J Theor Biol. 2000; 207 129-143
- 43 Ron E, Gridley G, Hrubec Z, Page W, Arora S, Fraumeni J F Jr. Acromegaly and gastrointestinal cancer. Cancer. 1991; 68 1673-1677
- 44 Popovic V, Damjanovic S, Micic D. et al . Increased incidence of neoplasia in patients with pituitary adenomas. The Pituitary Study Group. Clin Endocrinol (Oxf). 1998; 49 441-445
- 45 Mestrón A, Webb S M for the SEEN (Sociedad Española de Endcorinología y Nutrición). Spanish Acromegaly Registrer (Registro Español de Acromegalia - REA): Regional prevalence, morbidity and mortality. San Francisco; Endocrine Society June 2002 (Abstract). (Plus personal communication with DR Susan Webb)
- 46 Jenkins P J, Besser M. Acromegaly and cancer: a problem. J Clin Endocrinol Metab. 2001; 86 2935-2941
- 47 Renehan A G, O'Dwyer S T, Shalet S M. Colorectal neoplasia in acromegaly: the reported increased prevalence is overestimated. Gut. 2000; 46 440-441
- 48 Renehan A G, O'Dwyer S T, Shalet S M. Screening colonoscopy for acromegaly in perspective. Clin Endocrinol (Oxf). 2001; 55 731-733
- 49 Renehan A G, Shalet S M. Acromegaly and colorectal cancer: risk assessment should be based on population-based studies. J Clin Endocrinol Metab. 2002; 87 1909
- 50 Bari D, Gridley G, Ron E. et al . Acromegaly and cancer risk: a cohort study in Sweden and Denmark. Cancer Causes Control. 2002; 13 395-400
- 51 Melmed S. Acromegaly and cancer: not a problem?. J Clin Endocrinol Metab. 2001; 86 2929-2934
- 52 Perry I, Stewart P M, Kane K. Colorectal screening guidelines in acromegaly. Gut. 2003; 52 1387
- 53 Ho K Y, Weissberger A J. Characterization of 24-hour growth hormone secretion in acromegaly: implications for diagnosis and therapy. Clin Endocrinol Oxf. 1994; 41 75-83
- 54 Corpas E, Harman S M, Blackman M R. Human growth hormone and human aging. Endocr Rev. 1993; 14 20-39
- 55 Clayton R N, Stewart P M, Shalet S M, Wass J A. Pituitary surgery for acromegaly. Should be done by specialists [editorial]. BMJ. 1999; 319 588-589
- 56 Lincoln D T, Kaiser H E, Raju G P, Waters M J. Growth hormone and colorectal carcinoma: localization of receptors. In Vivo. 2000; 14 41-49
- 57 Thomas M J. The molecular basis of growth hormone action. Growth Horm IGF Res. 1998; 8 3-11
- 58 Ross R J. The GH receptor and GH insensitivity. Growth Horm IGF Res. 1999; 9 (Suppl B) 42-45; discussion 45 - 46
-
59 Lund P K.
IGFs and the digestive tract. In: Rosenfeld RG, Roberts CT Jr (eds) The IGF System. Molecular Biology, Physiology, and Clinical Applications. Totowa; Humana Press 1999: 517-544 - 60 Maison P, Balkau B, Simon D, Chanson P, Rosselin G, Eschwege E. Growth hormone as a risk for premature mortality in healthy subjects: data from the Paris prospective study. BMJ. 1998; 316 1132-1133
- 61 Le Marchand L, Donlon T, Seifried A, Kaaks R, Rinaldi S, Wilkens L R. Association of a common polymorphism in the human GH1 gene with colorectal neoplasia. J Natl Cancer Inst. 2002; 94 454-460
- 62 Bustin S A, Jenkins P J. The growth hormone-insulin-like growth factor-I axis and colorectal cancer. Trends Mol Med. 2001; 7 447-454
- 63 Webb S M, Casanueva F, Wass J A. Oncological complications of excess GH in acromegaly. Pituitary. 2002; 5 21-25
- 64 Rajasoorya C, Holdaway I M, Wrightson P, Scott D J, Ibbertson H K. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf). 1994; 41 95-102
- 65 Wass J A, Clemmons D R, Underwood L E, Barrow I, Besser G M, Van Wyk J J. Changes in circulating somatomedin-C levels in bromocriptine-treated acromegaly. Clin Endocrinol (Oxf). 1982; 17 369-377
- 66 Dobrashian R D, DJ O H, Hunt A, Beardwell C G, Shalet S M. Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly. Clin Endocrinol Oxf. 1993; 38 589-593
- 67 Parkinson C, Renehan A G, Ryder W D, O'Dwyer S T, Shalet S M, Trainer P J. Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly. Clin Endocrinol (Oxf). 2002; 57 59-64
- 68 Pollak M. Insulin-like growth factor physiology and cancer risk. Eur J Cancer. 2000; 36 1224-1228
- 69 Ma J, Pollak M N, Giovannucci E. et al . 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. 1999; 91 620-625
- 70 Giovannucci E, Pollak M N, Platz E A. et al . 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. 2000; 9 345-349
- 71 Kaaks R, Toniolo P, Akhmedkhanov A. et al . Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst. 2000; 92 1592-1600
- 72 Probst Hensch N M, Yuan J M, Stanczyk F Z, Gao Y T, Ross R K, Yu M C. IGF-1, IGF-2 and IGFBP-3 in prediagnostic serum: association with colorectal cancer in a cohort of Chinese men in Shanghai. Br J Cancer. 2001; 85 1695-1699
- 73 Palmqvist R, Hallmans G, Rinaldi S. et al . 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. 2002; 50 642-646
- 74 Renehan A G, Egger M, Zwahlen M. et al . Insulin-like growth factor (IGF)-I, IGF binding protein-3 and cancer risk: a systematic review and meta-regression. Lancet (in press). ;
- 75 Renehan A G, Painter J E, Atkin W S, Potten C S, Shalet S M, O'Dwyer S T. High-risk colorectal adenomas and serum insulin-like growth factors. Br J Surg. 2001; 88 107-113
- 76 Paterson A C, Leeding K S, Bach L A, Baldwin G S, Macrae F A, Shulkes A. More about: 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. 2000; 92 1947-1950
- 77 Teramukai S, Rohan T, Lee K Y, Eguchi H, Oda T, Kono S. Insulin-like growth factor (IGF)-I, IGF-binding protein-3 and colorectal adenomas in Japanese men. Jpn J Cancer Res. 2002; 93 1187-1194
- 78 Jones J I, Clemmons D R. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995; 16 3-34
- 79 LeRoith D, Baserga R, Helman L, Roberts C T, Jr. Insulin-like growth factors and cancer. Ann Intern Med. 1995; 122 54-59
- 80 Khandwala H M, McCutcheon I E, Flyvbjerg A, Friend K E. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000; 21 215-244
- 81 Furstenberger G, Senn H J. Insulin-like growth factors and cancer. Lancet Oncol. 2002; 3 298-302
- 82 Baserga R, Resnicoff M CDA, Valentinis B. The role of the IGF-I receptor in apoptosis. Vitam Horm. 1997; 53 65-98
- 83 Adenis A, Peyrat J P, Hecquet B. et al . Type I insulin-like growth factor receptors in human colorectal cancer. Eur J Cancer. 1995; 31a 50-55
- 84 Zenilman M E, Graham W. Insulin-like growth factor I receptor messenger RNA in the colon is unchanged during neoplasia. Cancer Invest. 1997; 15 1-7
- 85 Mishra L, Bass B, Ooi B S, Sidawy A, Korman L. Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers. Growth Horm IGF Res. 1998; 8 473-479
- 86 Freier S, Weiss O, Eran M. et al . Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon. Gut. 1999; 44 704-708
- 87 Hakam A, Yeatman T J, Lu L. et al . Expression of insulin-like growth factor-1 receptor in human colorectal cancer. Hum Pathol. 1999; 30 1128-1133
- 88 Lahm H, Amstad P, Wyniger J. et al . Blockade of the insulin-like growth-factor-I receptor inhibits growth of human colorectal cancer cells: evidence of a functional IGF-II-mediated autocrine loop. Int J Cancer. 1994; 58 452-459
- 89 Desbois-Mouthon C, Cadoret A, Blivet-Van Eggelpoel M J. et al . Insulin and IGF-1 stimulate the beta-catenin pathway through two signalling cascades involving GSK-3beta inhibition and Ras activation. Oncogene. 2001; 20 252-259
- 90 Playford M P, Bicknell D, Bodmer W F, Macaulay V M. Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Proc Natl Acad Sci U S A. 2000; 97 12 103-12 108
- 91 Jenkins P J, Frajese V, Jones A M. et al . Insulin-like growth factor I and the development of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000; 85 3218-3221
- 92 Potten C S, Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990; 110 1001-1020
- 93 van de Wetering M, Sancho E, Verweij C. et al . The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002; 111 241-250
- 94 Renehan A G, Booth C, Potten C S. What is apoptosis, and why is it important?. BMJ. 2001; 322 1536-1538
- 95 Renehan A G, Bach S P, Potten C S. The relevance of apoptosis for cellular homeostasis and tumorigenesis in the intestine. Can J Gastroenterol. 2001; 15 166-176
- 96 Kim P J, Plescia J, Clevers H, Fearon E R, Altieri D C. Survivin and molecular pathogenesis of colorectal cancer. Lancet. 2003; 362 205-209
- 97 Bach S P, Renehan A G, Potten C S. Stem cells: the intestinal stem cell as a paradigm. Carcinogenesis. 2000; 21 469-476
- 98 Mills S J, Mathers J C, Chapman P D, Burn J, Gunn A. Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis. Gut. 2001; 48 41-46
- 99 Potten C S, Owen G, Hewitt D. et al . Stimulation and inhibition of proliferation in the small intestinal crypts of the mouse after in vivo administration of growth factors. Gut. 1995; 36 864-873
- 100 Cats A, Dullaart R P, Kleibeuker J H. et al . Increased epithelial cell proliferation in the colon of patients with acromegaly. Cancer Res. 1996; 56 523-526
- 101 Cats A, De Vries E G, Kleibeuker J H. Proliferation rate in hereditary nonpolyposis colon cancer [letter]. J Natl Cancer Inst. 1991; 83 1687-1689
- 102 Al-Termimi S, Stellini M, Jordan S. et al . Acromegaly is associated with increased colonic mucosal cellular proliferation which might account for their increased risk of colorectal neoplasia. Endocrine Society Abstracts. 1999; 1-575
- 103 Beentjes J A, van Gorkom B A, Sluiter W J, de Vries E G, Kleibeuker J H, Dullaart R P. One year growth hormone replacement therapy does not alter colonic epithelial cell proliferation in growth hormone deficient adults. Clin Endocrinol Oxf. 2000; 52 457-462
- 104 Kellett M, Potten C S, Rew D A. A comparison of in vivo cell proliferation measurements in the intestine of mouse and man. Epithelial Cell Biol. 1992; 1 147-155
- 105 Renehan A G, Painter J E, O'Halloran D. et al . Circulating insulin-like growth factor II and colorectal adenomas. J Clin Endocrinol Metab. 2000; 85 3402-3408
- 106 Renehan A G, Toogood A A, Ryder W D. et al . Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides. Clin Endocrinol (Oxf). 2001; 55 469-475
- 107 Juul A, Main K, Blum W F, Lindholm J, Ranke M B, Skakkebaek N E. The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients. Clin Endocrinol Oxf. 1994; 41 85-93
- 108 Rajaram S, Baylink D J, Mohan S. Insulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev. 1997; 18 801-831
- 109 Clemmons D R. Insulin-like growth factor binding proteins and their role in controlling IGF actions. Cytokine Growth Factor Rev. 1997; 8 45-62
- 110 Baxter R C. Signalling pathways involved in antiproliferative effects of IGFBP-3: a review. Mol Pathol. 2001; 54 145-148
- 111 Butt A J, Williams A C. IGFBP-3 and apoptosis - a license to kill?. Apoptosis. 2001; 6 199-205
- 112 Firth S M, Baxter R C. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002; 23 824-854
- 113 Baxter R C. Insulin-like growth factor (IGF) binding proteins: the role of serum IGFBPs in regulating IGF availability. Acta Paediatr Scand Suppl. 1991; 372 107-114; discussion 115
- 114 Lamson G, Giudice L C, Cohen P. et al . Proteolysis of IGFBP-3 may be a common regulatory mechanism of IGF action in vivo. Growth Regul. 1993; 3 91-95
- 115 Leal S M, Liu Q, Huang S S, Huang J S. The type V transforming growth factor beta receptor is the putative insulin-like growth factor-binding protein 3 receptor. J Biol Chem. 1997; 272 20 572-20 576
- 116 Weinzimer S A, Gibson T B, Collett-Solberg P F, Khare A, Liu B, Cohen P. Transferrin is an insulin-like growth factor-binding protein-3 binding protein. J Clin Endocrinol Metab. 2001; 86 1806-1813
- 117 Gui Y, Murphy L J. Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) binds to fibronectin (FN): demonstration of IGF-I/IGFBP-3/fn ternary complexes in human plasma. J Clin Endocrinol Metab. 2001; 86 2104-2110
- 118 Fowlkes J L, Serra D M. Characterization of glycosaminoglycan-binding domains present in insulin-like growth factor-binding protein-3. J Biol Chem. 1996; 271 14 676-14 679
- 119 Liu B, Lee H Y, Weinzimer S A. et al . Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis. J Biol Chem. 2000; 275 33 607-33 613
- 120 Muti P, Quattrin T, Grant B J. et al . Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomarkers Prev. 2002; 11 1361-1368
- 121 Krajcik R A, Borofsky N D, Massardo S, Orentreich N. Insulin-like growth factor I (IGF-I), IGF-binding proteins, and breast cancer. Cancer Epidemiol Biomarkers Prev. 2002; 11 1566-1573
- 122 Yu H, Jin F, Shu X O. et al . Insulin-like growth factors and breast cancer risk in Chinese women. Cancer Epidemiol Biomarkers. Prev.2002; 11 705-712
- 123 Ng E H, Ji C Y, Tan P H, Lin V, Soo K C, Lee K O. Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients. Ann Surg Oncol. 1998; 5 194-201
- 124 Firth S M, Fanayan S, Benn D, Baxter R C. Development of resistance to insulin-like growth factor binding protein-3 in transfected T47D breast cancer cells. Biochem Biophys Res Commun. 1998; 246 325-329
- 125 McCaig C, Perks C M, Holly J M. Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin. J Cell Sci. 2002; 115 4293-4303
- 126 Modric T, Silha J V, Shi Z. et al . Phenotypic manifestations of insulin-like growth factor-binding protein-3 overexpression in transgenic mice. Endocrinology. 2001; 142 1958-1967
- 127 Coulson V J, Wass J A, Abdulla A F, Cotterill A M, Holly J M. Insulin-like growth factor binding proteins (IGFBPs) in acromegaly. Growth Regul. 1991; 1 119-124
- 128 Leng S L, Leeding K S, Gibson P R, Bach L A. Insulin-like growth factor-II renders LIM 2405 human colon cancer cells resistant to butyrate-induced apoptosis: a potential mechanism for colon cancer cell survival in vivo. Carcinogenesis. 2001; 22 1625-1631
- 129 Hoeflich A, Fettscher O, Lahm H. et al . Overexpression of insulin-like growth factor-binding protein-2 results in increased tumorigenic potential in Y-1 adrenocortical tumor cells. Cancer Res. 2000; 60 834-838
- 130 Arai T, Busby W Jr, Clemmons D R. Binding of insulin-like growth factor (IGF) I or II to IGF-binding protein-2 enables it to bind to heparin and extracellular matrix. Endocrinology. 1996; 137 4571-4575
- 131 Michell N P, Langman M J, Eggo M C. Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers. Br J Cancer. 1997; 76 60-66
- 132 Hoeflich A, Reisinger R, Lahm H. et al . Insulin-like growth factor-binding protein 2 in tumorigenesis: protector or promoter?. Cancer Res. 2001; 61 8601-8610
- 133 Slootweg M C, Ohlsson C, Salles J P, de Vries C P, Netelenbos J C. Insulin-like growth factor binding proteins-2 and -3 stimulate growth hormone receptor binding and mitogenesis in rat osteosarcoma cells. Endocrinology. 1995; 136 4210-4217
- 134 O'Connell J, O'Sullivan G C, Collins J K, Shanahan F. The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med. 1996; 184 1075-1082
- 135 Nagata S, Golstein P. The Fas death factor. Science. 1995; 267 1449-1456
- 136 Shiraki K, Tsuji N, Shioda T, Isselbacher K J, Takahashi H. Expression of Fas ligand in liver metastases of human colonic adenocarcinomas. Proc Natl Acad Sci U S A. 1997; 94 6420-6425
- 137 Bennett M W, O'Connell J, Houston A. et al . Fas ligand upregulation is an early event in colonic carcinogenesis. J Clin Pathol. 2001; 54 598-604
- 138 Bennett M W, O'Connell J, O'Sullivan G C. et al . The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol. 1998; 160 5669-5675
- 139 Belluco C, Esposito G, Bertorelle R. et al . Fas ligand is up-regulated during the colorectal adenoma-carcinoma sequence. Eur J Surg Oncol. 2002; 28 120-125
- 140 Watson A J, Merritt A J, Jones L S. et al . Evidence of reciprocity of bcl-2 and p53 expression in human colorectal adenomas and carcinomas. Br J Cancer. 1996; 73 889-895
- 141 Reddy B S, Wynder E L. Large-bowel carcinogenesis: fecal constituents of populations with diverse incidence rates of colon cancer. J Natl Cancer Inst. 1973; 50 1437-1442
- 142 van der Werf S D, Nagengast F M, van Berge Henegouwen G P, Huijbregts A W, van Tongeren J H. Colonic absorption of secondary bile-acids in patients with adenomatous polyps and in matched controls. Lancet. 1982; i 759-762
- 143 Potter J D. Colorectal cancer: molecules and populations. J Natl Cancer Inst. 1999; 91 916-932
- 144 Bayerdorffer E, Mannes G A, Richter W O. et al . Increased serum deoxycholic acid levels in men with colorectal adenomas. Gastroenterology. 1993; 104 145-151
- 145 Bayerdorffer E, Mannes G A, Ochsenkuhn T, Dirschedl P, Paumgartner G. Variation of serum bile acids in patients with colorectal adenomas during a one-year follow-up. Digestion. 1994; 55 121-129
- 146 Bayerdorffer E, Mannes G A, Ochsenkuhn T, Dirschedl P, Wiebecke B, Paumgartner G. Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. Gut. 1995; 36 268-273
- 147 Ochsenkuhn T, Bayerdorffer E, Meining A. et al . Colonic mucosal proliferation is related to serum deoxycholic acid levels. Cancer. 1999; 85 1664-1669
- 148 Veysey M J, Thomas L A, Mallet A I. et al . Prolonged large bowel transit increases serum deoxycholic acid: a risk factor for octreotide induced gallstones. Gut. 1999; 44 675-681
- 149 Jenkins P K, Veysey M J, Thomas L A. et al . Increased serum deoxycholic acid levels in acromegalic patients with colorectal neoplasia. J Endocrinol. 1997; 152 (suppl) 74
- 150 Veysey M J, Malcolm P, Mallet A I. et al . Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial. Gut. 2001; 49 828-834
- 151 Colao A, Baldelli R, Marzullo P. et al . Systemic hypertension and impaired glucose tolerance are independently correlated to the severity of the acromegalic cardiomyopathy. J Clin Endocrinol Metab. 2000; 85 193-199
- 152 Ragozzino M, Melton L J 3rd, Chu C P, Palumbo P J. Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. J Chronic Dis. 1982; 35 13-19
- 153 La Vecchia C, Negri E, Decarli A, Franceschi S. Diabetes mellitus and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 1997; 6 1007-1010
- 154 Adami H O, McLaughlin J, Ekbom A. et al . Cancer risk in patients with diabetes mellitus. Cancer Causes Control. 1991; 2 307-314
- 155 Weiderpass E, Gridley G, Nyren O, Ekbom A, Persson I, Adami H O. Diabetes mellitus and risk of large bowel cancer [letter]. J Natl Cancer Inst. 1997; 89 660-661
- 156 Will J C, Galuska D A, Vinicor F, Calle E E. Colorectal cancer: another complication of diabetes mellitus?. Am J Epidemiol. 1998; 147 816-825
- 157 Hu F B, Manson J E, Liu S. et al . Prospective study of adult onset diabetes mellitus (type 2) and risk of colorectal cancer in women. J Natl Cancer Inst. 1999; 91 542-547
- 158 Nilsen T I, Vatten L J. Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis. Br J Cancer. 2001; 84 417-422
- 159 Stoll B A. Association between breast and colorectal cancers. Br J Surg. 1998; 85 1468-1472
- 160 Giovannucci E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr. 2001; 131 (Suppl) 3109s-3120s
- 161 Tran T T, Medline A, Bruce W R. Insulin promotion of colon tumors in rats. Cancer Epidemiol Biomarkers Prev. 1996; 5 1013-1015
- 162 Koohestani N, Tran T T, Lee W, Wolever T M, Bruce W R. Insulin resistance and promotion of aberrant crypt foci in the colons of rats on a high-fat diet. Nutr Cancer. 1997; 29 69-76
- 163 Rosen T, Bengtsson B A. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990; 336 285-288
- 164 Bates A S, Van't Hoff W, Jones P J, Clayton R N. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996; 81 1169-1172
- 165 Nilsson B, Gustavasson-Kadaka E, Bengtsson B A, Jonsson B. Pituitary adenomas in Sweden between 1958 and 1991: incidence, survival, and mortality. J Clin Endocrinol Metab. 2000; 85 1420-1425
- 166 Pei L, Melmed S. Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 1997; 11 433-441
- 167 Zhang X, Horwitz G A, Heaney A P. et al . Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab. 1999; 84 761-767
- 168 Heaney A P, Singson R, McCabe C J, Nelson V, Nakashima M, Melmed S. Expression of pituitary-tumour transforming gene in colorectal tumours. Lancet. 2000; 355 716-719
- 169 Zhang X, Horwitz G A, Prezant T R. et al . Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 1999; 13 156-166
- 170 Folkman J. The role of angiogenesis in tumor growth. Semin Cancer Biol. 1992; 3 65-71
- 171 Rowland R S, Bell G D. Non-radiological technique for 3D imaging of intestinal endoscopes: computerised graphical 3D representation of endoscope and skeleton. Med Biol Eng Comput. 1998; 36 285-290
- 172 Williams C B, Saunders B P, Bell G D, Bladen J S, Gillies D F, Guy C M. Real-time magnetic three-dimensional imaging of flexible endoscopy. Gastrointest Endosc Clin N Am. 1997; 7 469-475
- 173 Renehan A, Painter J E, Rowlands R S, Shalet S M, O’Dwyer S T, Bell G D. Growth hormone exposure in acromegaly and bowel lengths measured by magnetic endoscope imaging. Abstract in GH-IGF Res. 2002; 12 (Suppl A) 8
- 174 Luebeck E G, Moolgavkar S H. Multistage carcinogenesis and the incidence of colorectal cancer. Proc Natl Acad Sci U S A. 2002; 99 15 095-15 100
- 175 Moolgavkar S H, Luebeck E G. Multistage carcinogenesis: population-based model for colon cancer. J Natl Cancer Inst. 1992; 84 610-618
- 176 Ezzat S, Melmed S. Clinical review 18: Are patients with acromegaly at increased risk for neoplasia?. J Clin Endocrinol Metab. 1991; 72 245-249
- 177 Holly J M, Gunnell D J, Davey Smith G. Growth hormone, IGF-I and cancer. Less intervention to avoid cancer? More intervention to prevent cancer?. J Endocrinol. 1999; 162 321-330
- 178 Shalet S M, Brennan B M, Reddingius R E. Growth hormone therapy and malignancy. Horm Res. 1997; 48 (Suppl 4) 29-32
- 179 Shalet S M, Brennan B M. Growth and growth hormone status following treatment for childhood leukaemia. Horm Res. 1998; 50 1-10
- 180 Swerdlow A J, Higgins C D, Adlard P, Preece M A. Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959 - 85: a cohort study. Lancet. 2002; 360 273-277
- 181 Ziel F H, Peters A L. Acromegaly and gastrointestinal adenocarcinomas. Ann Intern Med. 1988; 109 514-515
- 182 Sonksen P, Jacobs H, Orme S, Belchetz P. Acromegaly and colonic cancer. Clin Endocrinol Oxf. 1997; 47 647-648
- 183 de Herder W W, van der Lely A J, Lamberts S W. Colorectal cancer screening in acromegaly. Still many unresolved questions. Clin Endocrinol Oxf. 1997; 47 644-646
- 184 Jenkins P J, Fairclough P D. Screening guidelines for colorectal cancer and polyps in patients with acromegaly. Gut. 2002; 51 (Suppl 5) V13-V14
- 185 Renehan A G, O'Dwyer S T, Shalet S M. Guidelines for colonoscopic screening in acromegaly are inconsistent with those for other high risk groups. Gut. 2003; 52 1071-1072
- 186 Winawer S J, Fletcher R H, Miller L. et al . Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology. 1997; 112 594-642
- 187 Winawer S, Fletcher R, Rex D. et al . Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology. 2003; 124 544-560
- 188 Jarvinen H J, Mecklin J P, Sistonen P. Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 1995; 108 1405-1411
- 189 Jarvinen H J, Aarnio M, Mustonen H. et al . Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 2000; 118 829-834
- 190 Fuchs C S, Giovannucci E L, Colditz G A, Hunter D J, Speizer F E, Willett W C. A prospective study of family history and the risk of colorectal cancer. N Engl J Med. 1994; 331 1669-1674
- 191 Dunlop M G. Guidance on large bowel surveillance for people with two first degree relatives with colorectal cancer or one first degree relative diagnosed with colorectal cancer under 45 years. Gut. 2002; 51(Suppl 5) V17-20
- 192 Dunlop M G. Guidance on gastrointestinal surveillance for hereditary non-polyposis colorectal cancer, familial adenomatous polypolis, juvenile polyposis, and Peutz-Jeghers syndrome. Gut. 2002; 51 (Suppl 5) V21-27
- 193 Rhodes J M. Colorectal cancer screening in the UK: Joint Position Statement by the British Society of Gastroenterology, The Royal College of Physicians, and The Association of Coloproctology of Great Britain and Ireland. Gut. 2000; 46 746-748
- 194 Renehan A G, O'Dwyer S T, Shalet S M. Screening colonoscopy for acromegaly in perspective. Clin Endocrinol (Oxf). 2001; 55 731-733
- 195 Schoen R E, Corle D, Cranston L. et al . Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy? The Polyp Prevention Trial. Gastroenterology. 1998; 115 533-541
- 196 Rembold C M. Number needed to screen: development of a statistic for disease screening. BMJ. 1998; 317 307-312
- 197 Dunlop M, Campbell H. Screening for people with a family history of colorectal cancer. BMJ. 1997; 314 1779-1780
Dr. A. Renehan
Department of Surgery · Christie Hospital NHS Trust
Wilmslow Road · Manchester · M20 4BX · UK
Telefon: +44(161)4463363
Fax: +44(161)4463772
eMail: arenehan@picr.man.ac.uk