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Biomedical subjects

P Stattin

Publications and source records attributed to P Stattin.

At least 19 recordsLinked to original sources

Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women.

OBJECTIVE: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulin-like growth factor-I (IGF-I), and its binding protein (IGFBP)-3. DESIGN: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzyme-linked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. RESULTS: Adjusted mean serum IGF-I values were lower in women with BMI<22.5 kg/m(2) or BMI>29.2 kg/m(2) compared to women with BMI within this range (P(heterogeneity)<0.0001, P(trend)=0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P (trend)=0.005). CONCLUSIONS: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to non-obese women and inversely related to central adiposity.

Adult↗

Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women.

OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.

Adult↗

Interrelationships between plasma testosterone, SHBG, IGF-I, insulin and leptin in prostate cancer cases and controls.

Despite strong indirect evidence that androgens stimulate prostate cancer development, data from most analytical studies on this association have been negative. To further investigate this issue, we studied the interrelationships between androgenicity and insulin-like growth factor I (IGF-I), insulin and leptin. Within a prospective cohort study, we measured testosterone, sex hormone-binding globulin (SHBG) and IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, insulin and leptin, in plasma from 149 cases and 298 controls. Testosterone correlated positively with SHBG, whereas testosterone and SHBG correlated inversely with IGF-I, IGFBP-3, insulin, leptin and body mass index (BMI). Indices of free testosterone showed an inverse linear correlation with leptin (P<0.01), and a strong drop in the 5th quintile of BMI. However, levels of free testosterone showed non-linear relationships over quintiles of insulin and IGF-I, with a significant increase in the second quintile of IGF-I compared with other levels. The absence of an association between plasma levels of androgens and prostate cancer risk in analytical studies, despite the strong indirect evidence of their tumour-stimulating effects, may reflect the complex and mostly inverse associations of androgenicity to IGF-I, insulin and leptin which are hormones that have also been implicated as risk factors for prostate cancer.

Body Mass Index↗

Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer.

The short-term effects of rye bran bread intake in prostate cancer were investigated. Ten men with conservatively treated prostate cancer were randomised to a daily supplement of 295 g of rye bran bread and eight men to 275 g of wheat bread (control) with similar fibre content for three weeks. Blood samples, ultrasound-guided core biopsies of the prostate, and urine samples were taken. In the rye group, there was a significant increase in plasma enterolactone, and the apoptotic index increased significantly from 2.1% (SD 1.3) to 5.9% (SD 1.8), P<0.005 as measured by a TUNEL index in four cases in the rye group and seven cases in the control group. Besides a significant decrease in weight in both groups, only small changes were observed in plasma concentrations of prostate specific antigen (PSA), circulating sex hormones, excreted oestrogens, insulin-like growth factor (IGF)-I, and in the endothelial fibrinolytical system. High intake of rye bran bread is suggested to increase apoptosis in prostate tumours.

Aged↗

Prognostic value of the Gleason score in prostate cancer.

OBJECTIVE: To investigate the prognostic value of the Gleason score in prostate cancer. PATIENTS AND METHODS: A consecutive series of 305 men with prostate cancer diagnosed at transurethral resection (1975-1990) and with no curative treatment was analysed. There was no assessment of prostate-specific antigen level during this period. The mean (range) age at diagnosis was 73.7 (52-95) years and the mean follow-up was 6.4 (0-22) years. The influence of Gleason score and the percentage of the specimen area with tumour (% cancer) on disease-specific survival were assessed using Kaplan-Meier analyses. RESULTS: Of 305 cancers, 22% had a Gleason score of 4-5, 29% of 6, 18% of 7 and 32% of 8-10. At the follow-up, 89% of the men had died, of whom 42% had died from prostate cancer. The disease-specific 10-year survival was 56%. The disease-specific mean survival (DSMS) for Gleason score 4-5, 6, 7 and 8-10 was 20, 16, 10 and 5 years, respectively (P < 0.001). The DSMS did not differ significantly between Gleason 4 and 5 or between 8-10. There was a trend towards shorter survival for Gleason 4 + 3=7 (DSMS 9 years) than GS 3 + 4=7 (DSMS 13 years; P = 0.16). Gleason score and % cancer were independent predictors of DSMS (P < 0.001). CONCLUSION: The long-term prognosis of prostate cancer on deferred treatment is predicted well by the Gleason score. Four prognostic categories of prostate cancer are suggested, i.e. Gleason score 4-5, 6, 7 and 8-10.

Aged↗

Meat consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts: results from 24-hour dietary recalls.

OBJECTIVE: To evaluate meat intake patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts. DESIGN AND SETTING: 24-Hour dietary recalls were assessed within the framework of a prospective cohort study in 27 centres across 10 European countries by means of standardised computer-assisted interviews. SUBJECTS: In total, 22 924 women and 13 031 men aged 35-74 years. RESULTS: Mean total meat intake was lowest in the 'health-conscious' cohort in the UK (15 and 21 g day-1 in women and men, respectively) and highest in the north of Spain, especially in San Sebastian (124 and 234 g day-1, respectively). In the southern Spanish centres and in Naples (Italy), meat consumption was distinctly lower than in the north of these countries. Central and northern European centres/countries showed rather similar meat consumption patterns, except for the British and French cohorts. Differences in the intake of meat sub-groups (e.g. red meat, processed meat) across EPIC were even higher than found for total meat intake. With a few exceptions, the Mediterranean EPIC centres revealed a higher proportion of beef/veal and poultry and less pork or processed meat than observed in central or northern European centres. The highest sausage consumption was observed for the German EPIC participants, followed by the Norwegians, Swedish, Danish and Dutch. CONCLUSIONS: The results demonstrate distinct differences in meat consumption patterns between EPIC centres across Europe. This is an important prerequisite for obtaining further insight into the relationship between meat intake and the development of chronic diseases.

Adult↗

Transrectal core biopsy trauma may increase cell proliferation in prostate tumors.

Whilst analyzing the morphological effects of a 3-week dietary intervention in patients with prostate cancer, we made an unexpected observation to the effect that prostate biopsy trauma may, at least transiently, increase prostate tumor cell proliferation. Further studies are needed to evaluate the clinical significance of this observation.

Biopsy, Needle↗

Gonadotropin-releasing hormone receptor expression in the human prostate.

BACKGROUND: Inhibitory effects of gonadotropin-releasing hormone (GnRH) analogs on prostate cancer cell proliferation, both in vivo and in vitro, indicate the presence of specific binding sites for GnRH on prostate cancer cells. To investigate this issue further, we examined the expression of GnRH receptor (GnRH-R) mRNA and protein in human prostate biopsies as well as in other extrapituitary tissues. METHODS: The relative quantity of GnRH-R mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) in human prostate biopsies. Extrapituitary GnRH-R levels were determined by a semiquantitative PCR reaction. RESULTS: Using PCR, a relatively high expression level of GnRH-R mRNA was found in prostate tumor tissue followed by normal prostate, thymus, and kidney expression levels. The levels showed by heart, brain, placenta, lung, liver, skeletal muscle, pancreas, colon, ovary, small intestine, spleen, and testis were low but detectable, whereas peripheral blood leukocyte showed no demonstrable product. GnRH-R immunoreactivity was localized in both luminal and basal epithelial cells in benign and malignant prostate tissue, and GnRH-R were also observed in intraprostatic lymphocytes. The relative GnRH-R mRNA levels in prostate biopsies from 16 patients showed a wide range of individual differences, but these differences were not related to histological grade. Castration therapy did not significantly influence GnRH-R mRNA expression in normal and malignant prostate tissue. CONCLUSIONS: These results suggest that epithelial cells and infiltrating lymphocytes are targets for GnRH action in the human prostate. Comparative data show relatively high GnRH-R expression in human prostate tissue compared to other human tissues.

Aged↗

Plasma prolactin and prostate cancer risk: A prospective study.

Prolactin, a pituitary peptide hormone with multiple effects, stimulates prostate growth in experimental models. In humans, prolactin receptors are present in the prostate and are particularly abundant in pre-cancerous lesions. This suggests that prolactin could also be involved in the development of prostate cancer. In this study, we tested the hypothesis that elevated levels of circulating prolactin are associated with an increase in prostate cancer risk. We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort using plasma samples collected from 29,560 men at a health survey. We measured prolactin in plasma from 144 men who had a diagnosis of prostate cancer after a median follow-up time of 4 years after health survey and from 289 controls matched for age and date of recruitment. Risk was not associated with plasma prolactin levels in univariate regression analysis. Odds ratios of prostate cancer for increasing quartiles of prolactin were 1.0, 0.92 (95% CI 0.51-1.65), 0.82 (0.45-1.51) and 0.85 (0.49-1.47). Relative risk estimates remained unchanged after adjustments for height and weight or for plasma levels of testosterone, sex hormone-binding globulin, IGF-I and IGF-binding protein-3. Elevated circulating levels of prolactin were not related to an increase in prostate cancer risk, indicating that high circulating prolactin is not associated with development of prostate cancer.

Adult↗

Castration-induced reduction of vascular endothelial growth factor expression in benign human prostate tissue is lost in advanced prostate cancer.

OBJECTIVE: To determine the role of vascular response in the castration-induced regression of benign and malignant human prostate tissue, as recent studies show that castration rapidly decreases blood flow and induces endothelial cell death, which may be important for subsequent epithelial cell death and involution of the glandular tissue of the prostate. MATERIALS AND METHODS: The expression of vascular endothelial growth factor (VEGF) and its receptors was analysed using the quantitative reverse transcriptase-polymerase chain reaction, in benign and tumour areas of core biopsies taken before, and approximately 1 week after castration therapy. The castration-induced VEGF response was related to therapy-induced changes in tumour cell apoptotic index and subsequent response in serum prostate-specific antigen (PSA). In another set of patients, serum VEGF was quantified by enzyme-linked immunosorbent assay before, and at 3--6 months after castration therapy. RESULTS: VEGF mRNA was down-regulated after castration in benign prostate tissue (P < or = 0.05), whereas in tumour tissue, VEGF levels were reduced in some of the patients but unchanged or increased in others. In most patients whose tumour tissue responded with VEGF reduction, there was a corresponding increase in tumour cell apoptosis. Serum VEGF levels were not significantly changed after castration. Almost all patients responded with a substantial reduction in serum PSA after castration. CONCLUSION: Castration reduces VEGF mRNA expression in benign prostate tissue and generally in those prostate tumours where castration also induces tumour cell apoptosis. This suggests that a therapy-induced down-regulation of VEGF could be important for tumour cell death.

Apoptosis↗

p53 expression in correlation to clinical outcome in patients with renal cell carcinoma.

OBJECTIVE: The aim of this study was to evaluate the role of p53 as prognostic factor in renal cell carcinoma (RCC) and its relation to clinicopathological factors. MATERIAL AND METHODS: The nuclear accumulation of p53 protein was determined by immunohistochemical analysis in RCC specimens from 90 patients and was correlated with clinical stage, grade, DNA ploidy, S-phase fraction and cancer-specific survival. RESULTS: p53 overexpression was observed in 17 of 90 (19%) tumours. There was a significant correlation to stage (p = 0.016) and grade (p = 0.020) but not to DNA ploidy or S-phase. Patients with high p53 immunoreactivity had shorter cancer-specific survival (p = 0.003) than those with normal p53 protein expression. This difference was found in papillary and chromophobe tumour types (p < 0.0001) but not in conventional RCC. CONCLUSIONS: In patients with RCC, significant correlations between p53 protein expression and tumour stage, grade and survival time were observed. For patients with chromophobe and papillary tumour types, but not in conventional RCC, p53 immunoreactivity gave prognostic information, suggesting that the prognostic differences in p53 immunoreactivity might be due to disparate genetic abnormalities in the different RCC types.

Adult↗

Circulating insulin-like growth factor-I and benign prostatic hyperplasia--a prospective study.

OBJECTIVE: The aim of this study was to investigate the role of insulin-like growth factor-I (IGF-I), a strongly mitogenic and anti-apoptotic factor, in the development of benign prostatic hyperplasia (BPH). The bioactivity of IGF-I within tissues depends on circulating levels, as well as on the local production of IGF-I and the presence of IGF-binding proteins (IGFBPs). The IGFBPs regulate the efflux of IGF-I to the extravascular space and the bioavailability of IGF-I within tissues. MATERIAL AND METHODS: Within the Northern Sweden Health and Disease Study, 60 cases of BPH defined by a history of prostate resection were identified, and two controls per case were selected. IGF-I, IGFBP-1, IGFBP-3 and insulin were measured by immuno-radiometric assays in stored plasma samples drawn a mean of 3.2 years before surgery. RESULTS: The risk of BPH increased with increasing quartile levels of IGF-I adjusted for IGFBP-3 (p(trend) = 0.10) up to a relative risk of 2.16 (95% confidence interval 0.83-5.64) for the highest quartile. The risk decreased with increasing levels of IGFBP-1 (p(trend) = 0.10). CONCLUSIONS: Our results suggest that elevated IGF-I bioactivity may stimulate the development of BPH; however, they were not statistically significant and require confirmation from larger studies.

Humans↗

A cross-sectional study of IGF-I determinants in women.

Evidence is accumulating that elevated circulating insulin-like growth factor I (IGF-I) is related to increased cancer risk. The identification of hormonal, reproductive and lifestyle characteristics influencing its synthesis and bioavailability is of particular interest. Data from 400 women, who served as controls in two case-control studies nested within the same prospective cohort study, were combined. IGF-I, IGF-binding proteins 1, 2 and 3 (IGFBP-1, -2, -3) and insulin were measured in serum samples from all subjects and cotinine in 186 samples. Age appears to be the most important determinant of total IGF-I levels in women. Anthropometric measures, such as body mass index (BMI) or waist-to-hip ratio (WHR) do not seem to influence total IGF-I concentrations in peripheral blood, but may modulate IGF-I bioavailability through insulin-dependent changes in IGFBP-1 and -2 concentrations. Age at menarche, phase of the menstrual cycle at blood draw, parity, menopause, past oral contraceptive or hormone replacement therapy use, and tobacco smoking do not appear to exert an independent effect on IGF-I and its binding proteins. There was some suggestion that regular physical activity may increase total IGF-I and that women with positive family history of breast cancer might have higher IGF-I levels than those without such diagnosis in their relatives.

Age Factors↗

Ratios of IGF-I, IGF binding protein-3, and prostate-specific antigen in prostate cancer detection.

Recent studies have suggested that IGF-I and IGF-binding protein (IGFBP)-3, in combination with prostate-specific antigen (PSA), may enhance prostate cancer detection. In this study, we sought to determine the effect on the prediction of future prostate cancer occurrence by incorporating ratios of total and free PSA, IGF-I, IGFBP-3 into PSA testing. Within a population-based prospective cohort study, we investigated the validity (sensitivity and specificity) of plasma concentrations of total and free PSA, IGF-I, and IGFBP-3 and combinations thereof, in 114 cases and 97 controls, in the range of 1.75-13.5 microg/l for PSA, as used by Khosravi et al. (See Ref. 7 ). Validity estimated by the area under the curve in receiver operator characteristics analysis (with 95% confidence interval) for total PSA was 0.78 (range, 0.71-0.84); total/free PSA, 0.69 (range, 0.62-0.76); total PSA/IGF-I, 0.72 (range, 0.65-0.79); free PSA/IGF-I, 0.55 (range, 0.48-0.63); total PSA/IGFBP-3, 0.74 (range, 0.68-0.81); and free PSA/IGFBP-3, 0.57 (range, 0.49-0.64). Analysis of ratios of IGF-I, IGFBP-3, and free and total PSA did not improve validity of PSA testing in the prediction of future occurrence of prostate cancer. It is unlikely that these combinations will improve prostate cancer detection.

Biomarkers, Tumor↗

Leptin is associated with increased prostate cancer risk: a nested case-referent study.

A Western lifestyle has been implicated in the pathogenesis of prostate cancer. However, no clear association between obesity and prostate cancer has been shown. Leptin may stimulate prostate growth and angiogenesis, and receptors for leptin are present in the prostate. Leptin may, thus, be associated with increased risk of prostate cancer. One hundred forty-nine men with prostate cancer were identified (together with 298 matched referents) who, before diagnosis, had participated in population-based health surveys in Northern Sweden. Blood pressure, body mass index, and use of tobacco were recorded. Leptin, insulin, insulin-like growth factor I (IGF-I), IGF-I-binding proteins 1-3, testosterone, and sex hormone-binding globulin were analyzed in stored samples. Their influences on prostate cancer were estimated by conditional logistic regression analysis. Prostate cancer specimens were investigated for immunoreactivity for the leptin receptor. Relative risk (95% confidence intervals) estimates of prostate cancer over the quintiles of leptin were 1.0, 2.1 (1.1-4.1), 2.6 (1.4-4.8), 1.4 (0.7-2.7), and 1.6 (0.8-3.2). Adjustments for metabolic variables, testosterone, and IGF-I and its binding proteins did not attenuate this increased risk. Immunoreactivity for the leptin receptor was detected in normal, high-grade prostatic intraepithelial neoplasia lesions and malignant prostatic epithelium. Moderately elevated plasma leptin concentrations are associated with later development of prostate cancer. This may be due to direct effects of leptin on prostatic intraepithelial neoplasia lesions, or to indirect actions through other mechanisms. A critical fat mass related to an interior milieu favorable for prostate cancer development seems to exist, because intermediate but not high leptin levels are related to prostate cancer risk.

Adult↗

Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study.

BACKGROUND: Recent studies have suggested that men with elevated plasma levels of insulin-like growth factor-I (IGF-I) may have an increased risk of prostate cancer. Furthermore, IGF-binding proteins (IGFBPs) and insulin can modulate the activity of IGF-I. In this study, we sought to determine the role of IGF-I as well as IGFBPs-1, -2, and -3 and insulin as possible etiologic factors for prostate cancer. METHODS: We conducted a nested case-control study within the Northern Sweden Health and Disease Cohort Study. We measured levels of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and insulin in plasma samples from 149 men who had a diagnosis of prostate cancer between 1 month and 10 years after blood collection and among 298 control men. All statistical tests are two-sided. RESULTS: Case subjects had statistically significantly higher mean levels of IGF-I than control subjects (229 ng/mL; 95% confidence interval [CI] = 218-240 ng/mL] versus 214 ng/mL [95% CI = 208-221 ng/mL]; P =.02) and IGFBP-3 (2611 ng/mL [95% CI = 2518-2704 ng/mL] versus 2498 ng/mL [95% CI = 2437-2560 ng/mL]; P =.04). Conditional logistic regression analyses showed increases in prostate cancer risk with rising levels of IGF-I (P:(for trend) =.02) and IGFBP-3 (P(for trend) =.03). In case subjects younger than 59 years at the time of blood collection, the risk associated with increased IGF-I was higher (P:(for trend) =.01), whereas the risk associated with increased IGFBP-3 was lower (P(for trend) =.44) than the corresponding risks in the full cohort. Prostate cancer risk was not associated with levels of IGFBP-1, IGFBP-2, or insulin. CONCLUSIONS: Prostate cancer risk is increased in men with elevated plasma IGF-I. This association was particularly strong in younger men in this study, suggesting that circulating IGF-I may be specifically involved in the early pathogenesis of prostate cancer.

Age Factors↗