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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone and its principal mediator insulinlike growth factor I are known promoters of normal growth. To determine whether excessive secretion of growth hormone is associated with an increased occurrence of benign and of malignant tumors, we studied records of 87 patients with acromegaly seen in the Lahey Clinic Medical Center (Burlington, Mass) from 1957 to 1988 and compared the rate of tumor occurrence with a control group of patients with pituitary tumors (198) and with findings from a cancer registry. Patients with acromegaly had a 2.45-fold increased rate of malignant tumors (95% confidence interval, 0.98 to 5.04) compared with findings from the tumor registry. Female patients had a higher rate than male patients. The rate of carcinoma of the thyroid was excessive and previously underscribed, but the rate of carcinoma of the colon was not increased as reported by others. Among benign lesions, goiters, predominantly nodular, were seen in 25% of patients in addition to a large number of mesenchymal lesions.
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PMID:Benign and malignant tumors in patients with acromegaly. 167 93

A cohort of 1041 men who were discharged from the hospital with a diagnosis of acromegaly were examined for subsequent cancer. With a mean follow-up time of 8.3 years, an increased rate of cancers of the digestive organs was observed (27 cases; standard incidence ratio [SIR], 2.0; 95% confidence interval [CI], 1.3 to 2.9). Rates were elevated for cancers of the esophagus (7 cases; SIR, 3.1), stomach (4 cases; SIR, 2.5), and colon (13 cases; SIR, 3.1). The increased risk of colon cancer in acromegaly is consistent with previous clinical reports and suggests opportunities for etiologic research and early cancer detection. It would seem prudent to also evaluate this risk in current research on the use of growth hormone in older individuals to increase muscle mass and reduce body fat.
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PMID:Acromegaly and gastrointestinal cancer. 191 7

A cohort of 52 subjects diagnosed with acromegaly in southeastern Michigan and northern Ohio between 1935 and 1985 were followed to determine the incidence of colon cancer and polyps. Medical records were reviewed, subjects or their next-of-kin were interviewed, and screening examinations of the colon were offered to the living patients who were located. Data on demographics, personal histories of cancer and colon polyps, family history of colon cancer, and cure from acromegaly were obtained for both living and deceased subjects. The risk for colon cancer compared to the general population was estimated using standardized incidence ratios (SIRs). The expected number of cases was determined utilizing age, sex and race-specific rates provided by the cancer registry in southeastern Michigan. Among the 52 subjects, one could not be located and nine were deceased, none from colon cancer, with one known to have a history of colon polyps. Of 13 (31%) who declined the screening physical, one had a history of polyps and none reported a history of colon cancer. Two of 29 screened patients were found to have right-sided adenocarcinoma of the colon. Of the entire cohort, eight people (including one deceased) had a current or previous diagnosis of polyps, with five known to be histologically adenomatous. The SIR for colon cancer was 4.7 (95% confidence interval 0.6-17.1). Seven subjects, including the two with detected adenocarcinoma and four of the six living subjects with polyps only, reported a family history of colon cancer. The SIR for the subset of subjects with a family history of colon cancer was 29.1 (95% confidence interval of 3.5-104.6).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colon cancer and polyps in acromegaly: increased risk associated with family history of colon cancer. 233 12

The role of hormones and growth factors in the pathogenesis and therapy of colon cancer is biologically intricate and medically important. The effects of the previously described hormones and growth factors on normal and neoplastic colonic growth and development suggest the mechanisms by which hormonal alteration might either enhance or suppress the cancer process. The high degree of association between the specific endocrine-related processes (breast cancer, acromegaly, hyperparathyroidism, gastrin sensitivity of colon cancer, and cancer cell lines) suggests a significant role for hormones in colonic carcinogenesis. The relationship between the specific hormones and cancers is often unclear. This is the result of many factors: the variable presence of specific hormone receptors on the surface of the tumor or cell line; the inconsistent response to exogeneous hormone administration in vivo and in vitro; and the occasional failure of specific hormone-blocking agents to affect cell proliferation. The relationship between growth factors and cancers is also unclear. The following questions must be resolved in order to understand the significance of growth factors and the neoplastic process: (1) Is a growth factor significant in either an autocrine or a paracrine capacity? (2) Are combinations of growth factors rather than individual growth factors more biologically significant? (3) Do structural alterations of the immunologically similar, but functionally different growth factors modify their effect on the neoplastic tissue? The potential for manipulation of hormones and growth factors in the prevention and treatment of colon cancer is evidence to date suggesting that such efforts are indeed justified.
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PMID:Relationship of hormones and growth factors to colon cancer. 306 40

The occurrence of colon cancer in 1 patient with acromegaly prompted a study of an additional 12 patients with acromegaly. In addition to the index case, 1 patient was retrospectively discovered to have colon cancer, and 1 was found to have colonic adenocarcinoma in the course of the study. One patient had a presumptive sigmoid polyp shown by barium enema but refused further studies. Eight patients received colonoscopy. Two patients had adenomatous polyps and 1 had two hyperplastic polyps. This study supports previously published data on the occurrence of colon polyps in patients with acromegaly and suggests that the incidence of colon cancer is much higher than that expected by chance.
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PMID:Acromegaly and colon cancer. 648 93

Seventeen patients with acromegaly were prospectively studied with barium enemas and colonoscopy to investigate the possibility that acromegaly is associated with an increased frequency of colonic polyps and colon cancer. Polyps were identified in nine patients and were removed and examined in eight. In five patients the polyps were adenomatous, and in four of the five there were multiple polyps. The presence of polyps closely correlated with the presence of skin tags (p = 0.041) and also with the age of the patient (p less than 0.01). No new cases of colonic cancer were discovered; however, reviewing the records of 44 patients with acromegaly, four cases were previously diagnosed with colon carcinoma. This study identifies a unique group of patients that are at risk for the development of colonic polyps and perhaps colon cancer.
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PMID:Colonic polyps in patients with acromegaly. 709 3

Patients with acromegaly have a reduced life expectancy, with the accepted causes for premature death being vascular and respiratory disease. Increased mortality from malignant disease has also been reported. We, therefore, performed a multicenter retrospective cohort study of 1362 patients with acromegaly and investigated the relationships of mortality and cancer incidence with GH levels, duration of disease, and age at diagnosis. The overall cancer incidence rate [standardized incidence ratio, 0.76; 95% confidence interval (CI), 0.60-0.95] was lower than that in the general population of the United Kingdom, and there was no significant increase in site-specific cancer incidence rates. The overall cancer mortality rate was not increased, but the colon cancer mortality rate (standardized mortality ratio, 2.47; 95% CI, 1.31-4.22) was higher than expected. Mortality rates due to colon cancer, all malignant disease, cardiovascular disease and overall mortality were increased with higher posttreatment GH levels (P for trends, <0.02, <0.05, <0.02, and <0.0001). The overall mortality rate in patients with acromegaly with posttreatment GH levels less than 2.5 ng/mL (5 mU/L) was comparable to that in the general population of the United Kingdom (standardized mortality ratio, 1.10; 95% CI, 0.89-1.35). We conclude that high posttreatment GH levels are associated with an increased overall mortality rate and increased mortality rates due to colon cancer, cardiovascular disease, and all malignant disease. Posttreatment GH levels less than 2.5 ng/mL (5 mU/L) result in an overall mortality rate similar to that in the general population.
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PMID:Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. 970 39

Perturbations of the insulin-like growth factor (IGF) axis, including the autocrine production of IGFs, IGF binding proteins (IGFBPs) and IGFBP proteases such as prostate specific antigen (PSA), and cathepsin D have been identified in prostate, lung and breast cancer cells and tissues. Serum IGFBP-3 levels have been found to be negatively correlated to the risk of cancer. Interestingly, IGFBP-3 is a potent inhibitor of IGF action and also mediates apoptosis via an IGF-independent mechanism. Recent case-control studies have found an approximately 10% increase in the serum levels of IGF-I in patients with prostate, breast and lung cancers, which are among the most frequently diagnosed cancers. While the studies indicate an association between serum IGF-I levels and cancer risk, causality has not been established. Thus, serum IGF-I level may actually be a confounding variable, serving as a marker for autocrine tissue IGF-I production. Growth hormone (GH) therapy raises both IGF-I and IGFBP-3 levels in serum. However, the role of GH in controlling prostate, breast and lung growth and carcinogenesis remains unclear from animal studies. Increased GH levels as seen in acromegaly have been associated with benign prostatic hyperplasia but not with prostate, breast or lung cancers, although colon cancer mortality may be increased. Should serum IGF-I levels be proven to play a causal role in the pathogenesis of cancer, interpreting the risk associated with therapies such as GH replacement must take into account both the duration of exposure and the risk magnitude associated with the degree of serum IGF-I elevation. Since GH-deficient patients often have a subnormal IGF-I serum level, which normalizes on therapy, their cancer risk on GH therapy probably does not increase substantially above that of the normal population. Until further research in the area dictates otherwise, ongoing surveillance and routine monitoring of IGF-I levels in GH recipients should become standard of care.
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PMID:IGFs and human cancer: implications regarding the risk of growth hormone therapy. 1059 43

Neoplasms may be one of the systemic complications to which we attribute high mortality in acromegaly. The present study was designed to investigate the incidence of malignant tumors in patients with acromegaly in the Japanese population. In this report, 44 patients (25 men and 19 women) with biochemically proven acromegaly were studied retrospectively and had a total 670 patient years of the duration of acromegaly. We investigated the incidence of malignant tumors. There were 5 patients with malignant tumors (5 in men) in this study (11%). Male patients with acromegaly had nearly a 3.5 times higher ratio of malignancy than expected and this increased cancer incidence was considered significant (P=0.01). There was no significant increase in cancer incidence of either the total patient population or female patients. The malignant tumors were two thyroid cancers and one colon, one gastric and one bladder cancer. It is of note that the colon cancer of one patient was diagnosed 2 years after transsphenoidal surgery even though the levels of serum GH and insulin-like growth factor (IGF-1) were reduced to normal after operation. This preliminary study has suggested that male patients with acromegaly might have a high risk of malignancy and that careful screening for tumors is needed both before and after surgical and medical treatment, even in patients with normalized serum GH and IGF-1 levels.
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PMID:Incidence of malignant tumors in patients with acromegaly. 1089 Jan 85

Recent case-controlled studies have found increases in the serum levels of insulin-like growth factor-I (IGF-I) in subjects who had, or who eventually developed, prostate or premenopausal breast cancers. Since growth hormone (GH) increases IGF-I levels, concern has been raised regarding its potential role as a cancer initiation factor. The epidemiological studies, which indicate an association between serum IGF-I levels and cancer risk, have not established causality. In fact, several alternative explanations for the elevated serum IGF-I levels in cancer patients may be proposed based on human and animal models. First, an effect of IGF-I causing symptomatic benign tissue hyperplasia may result in an ascertainment bias leading to an initiation of procedures resulting in the diagnosis of asymptomatic cancers. Second, elevated serum IGF-I in cancer patients may originate within the tumor (as suggested by some animal studies). Thirdly, serum IGF-I may actually be a surrogate marker of tissue IGF-I levels or of nutritional factors, which are not under GH control and may be involved in cancer initiation. The role of GH in cancer initiation is further negated by the fact that in acromegaly, the incidence of cancer, other than possibly colonic neoplasia does not appear to be significantly increased. Furthermore, GH transgenic mice, with high IGF-I levels, do not develop breast, prostate, or colonic malignancies. It is known that IGFBP-3 can inhibit IGF action on cancer cells in vitro and also can induce apoptosis via an IGF-independent mechanism. Importantly, in addition to increasing IGF-I levels, GH also increases the serum levels of IGFBP-3 and serum IGFBP-3 levels have been shown to be negatively correlated with the risk of cancer in the above mentioned epidemiological studies and in a similar study on colon cancer. These studies suggest that cancer risk is increased in individuals in whom both high IGF-I levels and low IGFBP-3 levels are present. In subjects treated with GH, IGF-I and IGFBP-3 levels both rise together and are not within the elevated cancer-risk range, based on published studies. Long-term studies are needed to assess the potential risks, including the long-term cancer risk associated with GH therapy. These should take into account several factors, including the duration of exposure, the risk magnitude associated with the degree of serum IGF-I elevation, and the adjusted risk based on a concomitant increase in IGFBP-3 levels. Since GH treated patients often have sub-normal IGF-I serum levels, which normalize on therapy, one might predict that their cancer risk on GH therapy should not increase above the normal population. Until further research in the area dictates otherwise, on-going cancer surveillance and routine monitoring of serum IGF-I and IGFBP-3 levels in GH-recipients should be the standard of care. At present, the data that are available do not warrant a change in our current management of approved indications for GH therapy.
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PMID:Does the GH-IGF axis play a role in cancer pathogenesis? 1116 60


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