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Background: Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. Patients and methods: In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ER alpha(+) breast cancer and compared their IGF-1 blood levels with those of 178 ER alpha(+) and 83 ER alpha(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. Results: ER alpha(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ER alpha status of women with BBD was taken into account, the difference in IGF-1 levels between ER alpha(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ER alpha(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ER alpha(+) breast cancer patients were compared with ER alpha(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. Conclusion(s): We found evidence in support of an interaction of IGF-1 with the expression of ER alpha in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer.

Background: Limited information exists about the endocrine milieu of benign breast disease (BBD), a documented breast cancer risk factor. We compared blood levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1) between BBD patients by histological type and women without breast pathology. Methods: We studied 578 BBD patients and 178 healthy women in Athens, Greece, who provided blood samples, and completed interviewer-administered questionnaires. Results: Of the BBD patients, 254 had non-proliferative disease, 268 proliferative disease without atypia and 56 atypical hyperplasia. Comparing BBD patients with healthy women, the per cent differences (and 95% confidence intervals) for blood hormones, among pre-menopausal and peri/post-menopausal women, respectively, were: 22.4% (-4.0%, 56.1%) and 32.0% (5.6%, 65.1%) for estradiol; 26.2% (10.1%, 44.8%) and 30.9% (16.8%, 46.6%) for estrone; 19.5% (3.1%, 38.4%) and 16.5% (-5.0%, 42.9%) for testosterone; and -5.2% (-13.8%, 4.4%) and -12.1% (-19.8%, -3.6%) for IGF-1. Steroid hormones tended to be higher in proliferative compared with non-proliferative BBD. Conclusions: Circulating steroid hormones tend to be higher among women with BBD than women with no breast pathology and higher in proliferative than non-proliferative disease; these patterns are more evident among peri/post-menopausal women. In peri/post-menopausal women IGF-1 was lower among women with BBD compared with healthy women.

Benign breast disease (BBD), particularly proliferative BBD, is an established breast cancer risk factor. However, there has been no systematic attempt to compare the hormonal profiles of the two conditions. In a case-control investigation in Athens, Greece, we compared levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1), as well as their principal binding proteins, between breast cancer patients, women with BBD by histological type (proliferative and nonproliferative) and women with no breast pathology. We studied 466 women with incident breast cancer, 704 women with BBD and 244 healthy women. We used multiple regression to compare log-transformed serum hormone levels of breast cancer patients with those of healthy women and women with BBD by histological type (proliferative and nonproliferative BBD). The hormonal profile of breast cancer in our study was in line with the generally accepted hormonal profile of this disease, as reported from large cohort studies. Compared with healthy women, breast cancer patients tended to have higher levels of steroid hormones. The evidence was strong for estrone (difference 21.5%, P < 0.001), weaker for testosterone (difference 15.8%, P = 0.07) and weaker still for estradiol (difference 12.0%, P = 0.18). Also compared with healthy women, breast cancer patients had barely higher levels of IGF-1 (difference 2.0%, P = 0.51), but had significantly lower levels of IGF binding protein 3 (IGFBP-3) (difference -6.7%, P = 0.001). Compared with women with BBD, breast cancer patients had nonstatistically significantly lower levels of steroid hormones, but they had higher levels of IGF-1 [difference 5.5%, 95% confidence interval (CI) 0.7% to 10.6%] and lower levels of IGFBP-3 (difference -3.7%, 95% CI -6.7% to -0.7%). Differences were more pronounced when breast cancer patients were contrasted to women with proliferative BBD. Our findings suggest that high levels of IGF-1 may be an important factor toward the evolution of BBD to breast cancer.

The value of public sector information can be significantly increased by employing standards. For example, the use of a metadata standard for describing governmental resources allows citizens and businesses to locate and retrieve these resources in a more efficient and effective way. Furthermore, the use of a common document template for describing elementary and integrated public services (such as life events) can also substantially improve management and reuse of information and increase citizens' satisfaction. This paper proposes ametadata element set for governmental resources and a template for describing life events and public services. The proposed metadata element set can be used to facilitate the search and retrieval of governmental resources such as electronic documents. The proposed document template, termed the Governmental Markup Language (GovML), is a recommendation for describing public services and life events. It is anticipated that both public organizations and consumers of public services (citizens, businesses and other public organizations) would benefit from such a common information structure. Public authorities will be able to better manage (i.e., create, modify, store, etc.), exchange and reuse their information. Citizens and businesses will enjoy better services when searching for information regarding public services and life events. From amore technical perspective, GovML data vocabularies are proposed XML patterns, validated against an appropriate XML schema. Interoperability among public authorities is ensured as the rules that dominate the document syntax are common. Moreover, GovML-compliant information exploitsXMLpotential; thus it can be displayed in multiple formats and devices, such as Web browsers, PDAs and mobile phones. © 2004 by The Haworth Press, Inc. All rights reserved.

Adiponectin, an adipocyte-secreted hormone, is closely and inversely associated with insulin resistance and was recently found to be inversely and independently associated with endometrial cancer. Because insulin resistance in the setting of obesity has also been associated with the development of breast cancer, we have hypothesized that decreased adiponectin levels might underlie the association between breast cancer and obesity/insulin resistance. We evaluated the association of adiponectin with the occurrence of breast cancer in a case-control study comprising 174 women with newly diagnosed, histologically confirmed breast cancer and 167 controls. We found an inverse, fairly strong, and statistically significant association of serum adiponectin with breast cancer ( odds ratio, 0.84; 95% confidence interval, 0.71 - 0.99). Importantly, despite a fairly robust inverse association of adiponectin with breast cancer risk among postmenopausal women ( odds ratio, 0.82; 95% confidence interval, 0.67 - 1.00), no such significant association between adiponectin and breast cancer was found among premenopausal women. The observed associations were independent of possible effects of major components of the IGF system, leptin, body mass index, sociodemographic variables, and known risk factors for breast cancer. Future studies are needed to prove causality and provide further insights into both the mechanisms underlying the actions of this hormone and its potential role in breast cancer.

Background/Aims: Dehydroepiandrosterone (DHEA) is generally considered to have beneficial effects in humans. There is, however, limited information concerning the role of lifestyle variables, including diet, on blood DHEA levels. We have undertaken a study of DHEA determinants in a general population sample of adult Greeks. Methods: The sample consisted of 620 apparently healthy men and women aged 35-65 years, from all over Greece, participating in the EPIC study. Plasma DHEA was determined by radioimmunoassay. Nutritional intakes were ascertained through an interviewer-administered validated food frequency questionnaire, which also contained information on lifestyle variables. Statistical analyses were undertaken through simple cross-tabulations and by modelling the data through multiple regression. Results: DHEA declines sharply with age and there is some evidence that the decline may be sharper in men than in women. Protein intake was significantly inversely associated with plasma levels of DHEA, whereas other dietary factors, energy expenditure and anthropometric variables were unrelated to this hormone. Alcohol intake and tobacco smoking tended to be positively related to DHEA, but the respective associations were not statistically significant. Conclusion: There has been a growing interest in replacement of DHEA in ageing adults. If confirmed, our results would indicate that a reduction in protein intake could have qualitatively similar effects. Copyright © 2003 S. Karger AG, Basel.

Objectives: Insulin-like growth factor I (IGF-I) and other components of the IGF system have been implicated in the etiology of several human malignancies. We have undertaken a case-control study among Greek women to explore the relation of major components of the IGF system (IGF-I, IGF-II and IGF-binding protein 3, IGFBP-3) with endometrial cancer risk. Methods: During a 1-year period (1999), 84 incident cases of histologically confirmed endometrial cancer were compared with 84 control women admitted to the same clinical department for small gynecological operations, mainly pelvic prolapse. Data were modeled through multiple logistic regression. Results: Endometrial cancer was positively associated with IGF-II and inversely with IGF-I. Both associations were statistically significant and they appear symmetrical around the null value. IGFBP-3 is positively associated with endometrial cancer risk, but this association does not reach statistical significance. Conclusions: This study adds to the gradually developing consensus that components of the IGF system play a central role in human carcinogenesis. It is possible that IGF-II, rather than IGF-I, is closely linked to the etiology of endometrial cancer, the form of cancer most strongly associated with obesity.

Background/Aim: Because leptin is a hormone associated with obesity and reproduction, we attempted to examine whether there is a relationship between leptin and endometrial cancer. Methods: Cases were 84 women with histologically confirmed incident endometrial cancer, whereas controls were 84 women admitted to the same hospital for small surgical operations. The serum leptin levels were determined in fasting morning blood samples by using radioimmunoassay. The mean values of leptin levels among cases and controls were compared with simple t test, and the data were further analyzed using multiple logistic regression procedures. Results: The serum leptin levels were 36.7 +/- (SD) 25.7 ng/ml among cases and 26.9 +/- 19.8 ng/ml among controls (p = 0.006). After adjustment for known risk factors of endometrial cancer, components of the insulin-like growth factor system did not confound the association of leptin with endometrial cancer, but this association was eliminated, when the body mass index was adjusted for. Thus, the odds ratio for an increment of 1 SD of blood leptin was 1.52 (p = 0.03) before adjustment for body mass index, but only 1.13 (p = 0.62) after adjustment for it. Conclusions: In a case-control study of incident endometrial cancer in Greece, we found evidence that leptin is strongly positively associated with endometrial cancer. It cannot be conclusively inferred, however, whether leptin elevation, as a consequence of obesity, plays a role in endometrial carcinogenesis or whether it is a simple correlate of obesity. Copyright (C) 2002 S. Karger AG, Basel.

Objective: To investigate whether the three principal components of the insulin-like growth factor (IGF) system, IGF-1, IGF-2 and IGF binding protein-3 (IGFBP-3), are associated with survival from childhood leukemia. Patients and Methods: 116 children, 0-14 years old, with newly diagnosed and bone-marrow-biopsy-confirmed acute childhood leukemia between 1993 and 1996 were followed up until death or March 31, 1998. IGF-1, IGF-2 and IGFBP-3 were measured at diagnosis and clinical data, including presence of hepatosplenomegaly and number of white blood cells, were available. Results: After controlling for gender, age, indicators of clinical severity and the other measured components of the IGF system there was a statistically significant (p < 0.05) inverse association of IGFBP-3 with survival. An increment of one standard deviation in IGFBP-3 was associated with a 65% reduction of the death hazard among the children with leukemia. Neither IGF-1 nor IGF-2 was associated with survival in this data set. Conclusion: The presented empirical evidence in conjunction with the fact that IGFBP-3 modulates IGF-1 and IGF-2 bioavailability and is likely to have proapoptotic effects makes this compound a plausible independent predictor of survival from childhood leukemia. Copyright 2001 S. Karger AG, Basel.

Objectives To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin-like growth factor 1 (IGF-1). Patients and methods In the context of a case-control study, 112 men were admitted to three teaching hospitals in Athens, Greece, for disorders other than cancer. Sociodemographic data and detailed histories of smelting, alcohol and coffee consumption were recorded. A validated food-frequency questionnaire was administered by an interviewer and serological measurements of IGF-1 and its binding protein-3 conducted. Results IGF-1 declined significantly by almost 25% among men aged > 75 years and there was a small reduction in IGF-1 levels with increased alcohol intake, with a mean (95% confidence interval, CI) change of -1.6 (-2.2 to -0.9)% for an increment of one drink per day, There was no evidence for an effect of either smelting or coffee consumption on IGF-1 level. Among foods, the consumption of cooked tomatoes was substantially and significantly inversely associated with IGF-1 levels, with a mean (95% CI) change of -31.5 (-43.1 to -7.9)% for an increment of one serving per day. Conclusions The strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) and an important endocrine factor in the aetiology of this disease (IGF-1) seem to be related in a way that suggests that at least one, and perhaps more, exogenous factors in the development of prostate cancer may be mediated through the IGF-1 system.

There is substantial evidence linking steroid hormones and diet to cancer aetiology, The evidence on lifestyle determinants of steroid hormones, however, is limited. We have conducted a study to identify dietary and other lifestyle predictors of testosterone and oestradiol among adult men. Subjects were 112 healthy Greek men, recruited as controls in a case-control study on the aetiology of liver cancer. Demographic data and detailed histories of smoking habits and alcohol consumption were recorded. Diet was assessed through an interviewer-administered validated food-frequency questionnaire. Serologic measurements of oestradiol, testosterone and sex hormone binding globulin were also conducted. We developed linear regression models to evaluate the associations of smoking and dietary factors with serum testosterone and oestradiol, The results indicate that, among men, both testosterone and oestradiol serum levels decline with age, whereas body mass index may be inversely related with testosterone and positively with oestradiol. The evidence concerning alcohol in relation to these hormones is inconclusive, Emerging evidence concerning smoking suggests positive associations with both hormones in the blood. The principal nutritional findings are a positive association of carbohydrate intake with testosterone levels and a set of inverse associations of vitamins with oestradiol. (C) 2001 Lippincott Williams & Wilkins.

Objective: Liver disease in men has been associated with an imbalance of serum estradiol and testosterone. We have evaluated whether serum estradiol and testosterone levels are altered in male liver cancer patients as a result of a specific effect of the disease or because of the associated liver damage. Methods: We have performed a hospital-based case-control study in Greece. The study subjects were all men; 73 patients with hepatocellular carcinoma (HCC), 25 with metastatic liver cancer (MLC) patients and 111 control subjects. Serum estradiol, testosterone and sex hormone binding globulin (SHBG) levels were measured for each subject. Data were analyzed by multiple linear regression. Results: Mean serum estradiol levels were significantly higher among HCC patients as well as among patients with MLC compared to controls. Mean serum testosterone levels were significantly lower among HCC patients as well as among patients with MLC compared to controls. The mean SHBG levels did not differ significantly between the groups. After controlling for the degree of liver damage, the elevated serum estradiol and reduced serum testosterone levels among HCC and MLC patients were no longer significant. Conclusions: Changes in sex steroid levels among patients with liver damage are due to the liver damage per se and not to specific disease processes. Copyright (C) 2001 S. Karger AG, Basel.

Objectives: Because both breast cancer and the hormone leptin are associated with obesity and reproductive phenomena in women, we have examined whether there is a relationship between leptin and breast cancer among premenopausal and postmenopausal women. We have also evaluated in this dataset the association of IGF-I with breast cancer. Methods: Seventy-five cases, diagnosed during mammographic screening, with incident breast cancer were matched for age and type of permanent residence with seventy-five controls from those screened negative in the same study base. Results: There was no evidence for an association between IGF-I and either premenopausal or postmenopausal breast cancer risk or between leptin and postmenopausal breast cancer. Among premenopausal women, however, there was a strong and statistically significant inverse association of leptin with breast cancer. Conclusion: We did not confirm the positive association, reported from other investigations, of IGF-I with premenopausal breast cancer risk. We have found evidence, however, that leptin may be inversely related to breast cancer risk among premenopausal women. The latter finding is not biologically implausible and deserves to be examined in additional datasets.

Objective: Insulin-like growth factor-1 (IGF-1) and its principal binding protein-3 (IGFBP-3) are central in the mediation of the effect of growth hormone, and the IGF system has been reported to play a role in the pathogenesis of childhood leukemia. Methods: To further evaluate the hypothesis connecting the IGF system to this disease, we have examined whether IGF-1 and IGFBP-3 are associated with the two main endogenous risk factors for childhood leukemia, namely gender and birth weight, since boys and heavier newborns are known to be at higher risk. IGF-1 and IGFBP-3 were measured under code in the serum of 118 apparently healthy children aged 0-14years and the values of each of these components were regressed on age, gender and birth weight. Insulin-like growth factor-2 (IGF-2), as a dependent variable, and anemia during the corresponding pregnancy, as a predictor variable, were also evaluated for exploratory purposes. Results: In the total data set, IGF-1 was positively associated with birth weight (p = 0.0001), whereas girls had higher levels of IGFBP-3 (p = 0.01). Conclusions: It appears that the associations of measured components of the IGF system with the examined risk factors for childhood leukemia are largely compatible with those that would have been expected, if this system played a role in the pathogenesis of childhood leukemia.

The insulin-like growth factor (ICF) axis has important autocrine, paracrine, and endocrine roles in the promotion of growth. Alterations of the IGF system have recently been implicated in the pathogenesis of several malignancies, but the relation to hepatocellular carcinoma (HCC) risk is unclear. To address this issue, we used an immunoradiometric assay to quantify IGF-I levels in serum samples in a hospital-based, case-control study in Greece. The study subjects were all men and included 53 patients with HCC positive for hepatitis B and/or hepatitis C virus infections, 20 virus-negative HCC patients, 25 virus-negative patients with metastatic liver cancer (MLC), and I I I virus-negative control subjects. Data were analyzed by multiple linear regression, using IGF-I as the dependent variable. The mean value of IGF-I was 65.9 ng/ml among virus-positive HCC patients, 79.5 ng/ml among virus-negative HCC patients, 110.8 ng/ml among patients with MLC, and 174.7 ng/ml among hospital controls. After controlling for the degree of liver damage, as assessed by prothrombin time and serum albumin level, the reduction in IGF-I level among HCC patients was found to be more than could be attributed to liver damage alone. This finding may have both diagnostic and pathophysiological implications. Int. J. Cancer 87:118-121, 2000. (C) 2000 Wiley-Liss, Inc.

The aetiology of most cases of childhood leukaemia remains unknown, but several studies have indicated that increased birthweight and height are risk factors for the disease. Since insulin-like growth factor-I (IGF-I) mediates the effect of growth hormone and has been positively associated with prostate cancer, we have evaluated the role of this hormone and its principal binding protein, IGFBP-3, in the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from those recorded by a national network of childhood oncologists were enrolled in our study. Controls were children hospitalised for acute conditions of no more than moderate severity with matching for gender, age and maternal place of residence. Blood measurements of IGF-I and IGFBP-3 were undertaken using commercially available radioimmunoassays. Serum IGF-I values decreased by about 1.7% per month, and the rate of decline was higher, though not significantly so, among cases (2.1% per month) than among controls(1.4%). There was no significant association between IGF-I and the likelihood of childhood leukaemia, but an increment of I mu g/ml of IGFBP-3 was associated with a substantial and statistically significant reduction of childhood leukaemia by 28% (95% confidence interval 7% to 45%). Because IGFBP-3 is essentially a binding protein, we interpret our findings as indicating that bioavailable IGF-I may play an important role in the aetiology of childhood leukaemia. The much smaller quantities and the inherent instability of IGF-I in the blood in comparison to those of IGFBP-3 are likely to hinder documentation of an underlying positive association of IGF-I with the disease. (C) 1999 Wiley-Liss, Inc.