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  • 1
    Keywords: CANCER ; GROWTH ; GROWTH-FACTOR ; BLOOD ; COHORT ; DISEASE ; RISK ; PROTEIN ; RISK-FACTORS ; INTERVENTION ; BINDING ; ASSOCIATION ; BREAST-CANCER ; hormone ; HEALTH ; PLASMA ; AGE ; WOMEN ; MEN ; risk factors ; PRESSURE ; cholesterol ; GLUCOSE ; BLOOD-PRESSURE ; MYOCARDIAL-INFARCTION ; BODY ; HYPERTENSION ; PROJECT ; body mass index ; FACTOR-I ; CARDIOVASCULAR RISK-FACTORS ; BINDING PROTEIN ; insulin ; MASS INDEX ; IGF-I ; ASSOCIATIONS ; RE ; ARRAY ; CARDIOVASCULAR-DISEASE ; GROWTH-FACTOR-I ; LEVEL ; INTERVAL ; analysis ; methods ; HORMONES ; odds ratio ; BMI ; RISK-FACTOR ; CANCERS ; cross-sectional studies ; Aged ; IGFBP-1 ; IGFBP-3 ; NUTRITIONAL REGULATION ; cardiovascular disease ; cardiovascular risk factors ; COLORECTAL-CANCER RISK ; FACTOR-BINDING-PROTEINS ; insulin-like growth factor binding proteins ; Insulin-Like Growth Factor I ; ISCHEMIC-HEART-DISEASE ; LEFT-VENTRICULAR HYPERTROPHY
    Abstract: PURPOSE: Elevated circulating insulin-like growth factor I (IGF-I) levels increasingly are being implicated as a potential risk factor for the development of some cancers; however, relatively few epidemiologic Studies have focused on potential relationships between circulating IGF-I levels an cardiovascular risk factors or cardiovascular disease. Hence, our objective is to examine relationships between IGF-I levels; body mass index (BMI); fasting insulin level; IGF binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 levels; and an array of traditional cardiovascular risk factors. METHODS: Our analysis included 715 men and women aged 30 to 62 years who participated in the Vasterbotten Intervention Project cohort. IGF-1 and IGFBP-1, -2, and -3 were measured in stored plasma samples. Cardiovascular risk factors of interest included glucose level (fasting and 2-hour postload). lipid levels (total cholesterol, high-density lipoprotein cholesterol, and triglycerides), blood pressure (systolic and diastolic), and hypertension status. All presented results were adjusted for age, sex, and laboratory batch. RESULTS: IGF-1 quartile was associated inversely with 2-hour glucose level and diastolic blood pressure. There was a stepwise inverse graded association between increasing IGF-I quartile and hypertension, with an odds ratio of 0.51 (95% confidence interval, 0.29-0.90) for hypertension comparing the fourth IGF-I quartile with the first. Further adjusting for BMI and IGFBP-3 level simultaneously strengthened the inverse association, with an odds ratio of 0.42 (95% confiderice interval, 0.22-0.80) for hypertension comparing the fourth With the first IGF-I quartile. CONCLUSIONS: Contrary to positive associations between IGF-I levels and some cancers, Our results suggest that IGF-I level may be related inversely to prevalent hypertension, a risk factor for cardiovascular disease
    Type of Publication: Journal article published
    PubMed ID: 16431135
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  • 2
    Keywords: CANCER ; BLOOD ; CELL-PROLIFERATION ; MODEL ; COHORT ; DISEASE ; RISK ; tumour ; ASSOCIATION ; PROGRESSION ; resistance ; PLASMA ; AGE ; MEN ; PROSPECTIVE COHORT ; prostate cancer ; PROSTATE-CANCER ; SWEDEN ; HIGH-LEVEL ; leptin ; insulin ; IGF-I ; ONCOLOGY ; REGRESSION ; RADICAL PROSTATECTOMY ; development ; GROWTH-FACTOR-I ; LEVEL ; case control studies ; INTERVAL ; INSULIN-RESISTANCE ; BODY-MASS INDEX ; USA ; prospective ; prospective study ; STEROID-HORMONES ; odds ratio ; C-PEPTIDE ; ANDROGEN ; prostatic neoplasms ; LOGISTIC-REGRESSION ; GENERAL-POPULATION ; insulin resistance ; FASTING GLUCOSE ; TYPE-2 DIABETES-MELLITUS ; blood glucose ; META-REGRESSION ANALYSIS ; SERUM LEPTIN LEVELS
    Abstract: Factors related to insulin resistance have been implicated in prostate cancer development, however, few analytical studies support such an association. We performed a case control study on 392 prostate cancer cases and 392 matched controls nested in a prospective cohort in Northern Sweden. Plasma concentrations of C-peptide, leptin, glycated haemoglobin (HbA1c) and fasting and post-load glucose were analysed and homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Conditional logistic regression analyses were used to calculate odds ratios (OR) of prostate cancer. High levels of C-peptide, HOMA-IR, leptin and HbA1c were associated with significant decreases in risk of prostate cancer, with ORs for top vs. bottom quartile for C-peptide of 0.59 (95% Confidence Interval [CI], 0.40-0.89; p(trend) = 0.008), HOMA-IR 0.60 (95% CI, 0.38-0.94; p(trend) = 0.03), leptin 0.55 (95% CI, 0.36-0.84; p(trend) = 0.006) and HbA1c 0.56 (95% CI, 0.35-0.91; p(trend) = 0.02). All studied factors were strongly inversely related to risk among men less than 59 years of age at blood sampling, but not among older men, with a significant heterogeneity between the groups for leptin (p(heterogeneity) = 0.006) and fasting glucose (p(heterogeneity) = 0.03). C-peptide and HOMA-IR were strongly inversely related to non-aggressive cancer but were non-significantly positively related to risk of aggressive disease (p(heterogeneity) = 0.007 and 0.01, respectively). Our data suggest that androgens, which are inversely associated with insulin resistance, are important in the early prostate cancer development, whereas insulin resistance related factors may be important for tumour progression. (c) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17278097
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  • 3
    Keywords: CANCER ; tumor ; PROSTATE ; COHORT ; EPIDEMIOLOGY ; RISK ; METABOLISM ; TUMORS ; BINDING ; ASSOCIATION ; NO ; hormone ; PLASMA ; prostate cancer ; PROSTATE-CANCER ; SWEDEN ; cancer risk ; case-control studies ; HIGH-LEVEL ; SERUM ; case control study ; case-control study ; ASSOCIATIONS ; INCREASE ; TUMORIGENESIS ; RADICAL PROSTATECTOMY ; prospective studies ; LEVEL ; case control studies ; methods ; PLASMA-LEVELS ; USA ; HORMONES ; TESTOSTERONE ; prospective ; prospective study ; STEROID-HORMONES ; odds ratio ; CANCER-RISK ; CIRCULATING LEVELS ; ANDROGEN ; prostatic neoplasms ; androgens ; ENDOGENOUS SEX-HORMONES ; ANDROSTANEDIOL GLUCURONIDE ; FREE TESTOSTERONE ; PLASMA TESTOSTERONE
    Abstract: BACKGROUND. Androgens have been implicated in prostate tumorigenesis, but prospective studies have overall reported no association between circulating levels of androgens and risk of prostate cancer. However, some recent studies have shown that a high level of testosterone increase the risk of non-aggressive tumors but is associated with a decreased risk of aggressive tumors. METHODS. We prospectively measured plasma levels of total testosterone, androstanediol glucuronide (A-diol-g) and sex hormone binding globuline (SHBG) and calculated estimated levels of free testosterone, in a nested case-control study of 392 cases and 392 matched controls. RESULTS. None of the studied hormones were significantly associated with prostate cancer risk in the full study group or in subgroups according to tumor aggressiveness. Odds ratios in the full study group, for top versus bottom quartile, was for total testosterone 1.25 (95% Cl = 0.79-2.00; P-trend = 0.51); free testosterone, 1.31 (95% Cl = 0.82-2.07; P-trend = 0.35); A-diol-g, 0.88 (95% Cl = 0.59-1.33; P-trend = 0.77); and for SHBG, 1.01 (95% Cl = 0.64-1.58; P-trend = 0.94). CONCLUSIONS. We found no significant associations between androgen levels and risk of prostate cancer in this population-based, non-screened cohort. Prostate 67: 1230-1237, 2007. (c) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17562541
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  • 4
    Keywords: CANCER ; PROSTATE ; COHORT ; DISEASE ; RISK ; CELL-LINES ; ASSOCIATION ; ALPHA ; NO ; STAGE ; TRIAL ; prevention ; DESIGN ; DIFFERENCE ; PLASMA ; MEN ; smoking ; prostate cancer ; PROSTATE-CANCER ; cancer risk ; MULTIVARIATE ; case-control studies ; PREDICTORS ; EPIC ; nutrition ; NESTED CASE-CONTROL ; RELATIVE RISK ; VITAMIN-E ; case-control study ; GRADE ; SUPPLEMENTATION ; USA ; prospective ; CANCER-RISK ; ENGLAND ; SUBSEQUENT RISK ; DIETARY SELENIUM ; European Prospective Investigation into Cancer ; SERUM SELENIUM
    Abstract: Background: Some evidence indicates that a low selenium intake may be associated with an increased risk of prostate cancer. Objective: The aim of this study was to investigate the association of plasma selenium concentration with subsequent prostate cancer risk and to examine this association by stage and grade of disease and other factors. Design: A nested case-control study was performed among men in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between plasma selenium concentration and prostate cancer risk was assessed in 959 men with incident prostate cancer and 1059 matched controls. Results: Overall, plasma selenium concentration was not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of selenium concentration compared with the lowest fifth was 0.96 (95% CI: 0.70, 1.31; P for trend = 0.25). There were no significant differences in the association of plasma selenium with risk when analyzed by stage or grade of disease. Similarly, the association of selenium with risk did not differ by smoking status or by plasma alpha- or gamma-tocopherol concentration. Conclusion: Plasma selenium concentration was not associated with prostate cancer risk in this large cohort of European men. Am J Clin Nutr 2008; 88:1567-75
    Type of Publication: Journal article published
    PubMed ID: 19064517
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  • 5
    Keywords: ENERGIES ; CANCER ; Germany ; MODEL ; MODELS ; PROSTATE ; FOLLOW-UP ; INFORMATION ; COHORT ; RISK ; RISKS ; ASSOCIATION ; NO ; HEALTH ; PLASMA ; ENERGY ; AGE ; MEN ; PROSPECTIVE COHORT ; smoking ; prostate cancer ; PROSTATE-CANCER ; ethanol ; MULTIVARIATE ; RECRUITMENT ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; nutrition ; RELATIVE RISK ; ONCOLOGY ; WEIGHT ; ENERGY-INTAKE ; PHYSICAL-ACTIVITY ; HEIGHT ; biomarker ; USA ; cancer research ; RISK-FACTOR ; MIDDLE-AGED MEN ; energy intake ; WINE ; BEVERAGES
    Abstract: Alcohol is a risk factor for several types of cancer. However, the results for prostate cancer have been inconsistent, with most studies showing no association. Within the European Prospective Investigation into Cancer and Nutrition, detailed information were collected from 142,607 male participants on the intake of alcoholic beverages at recruitment (for 100% of the cohort) and over lifetime (for 76% of the cohort) between 1992 and 2000. During a median follow-up of 8.7 years, 2,655 prostate cancer cases were observed. Multivariate Cox proportional hazard models were used to examine the association of alcohol consumption at recruitment and average lifetime alcohol consumption with prostate cancer adjusted for age, center, smoking, height, weight, physical activity, and nonalcohol energy intake. Overall, neither alcohol consumption at baseline nor average lifetime alcohol consumption was associated with the risk for prostate cancer in this cohort of men. Men who consumed 〉= 60 g alcohol per day had a relative risk of 0.88 [95% confidence interval (95% CI) 0.72-1.081 compared with men with an intake of 0.1-4.9 g/d; the respective relative risk for average lifetime intake was 1.09 (95% CI, 0.86-1.39). For advanced prostate cancer (n=537), the relative risks for 〉= 60 and 0.1-4.9 g alcohol per day at baseline were 0.98 (95% CI, 0.66-1.44) and 1.28 (95% CI, 0.79-2-07), respectively, for average lifetime intake. No statistically significant association was observed for alcohol intake from specific alcoholic beverages. Our results indicate no association between the consumption of alcohol and prostate cancer in this cohort of European men
    Type of Publication: Journal article published
    PubMed ID: 18483352
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  • 6
    Keywords: CANCER ; DIAGNOSIS ; COHORT ; RISK ; ASSOCIATION ; breast cancer ; BREAST-CANCER ; WOMEN ; OBESITY ; SWEDEN ; POSTMENOPAUSAL WOMEN ; leptin ; IGF-I ; case-control study ; WEIGHT ; GROWTH-FACTOR-I ; OVERWEIGHT ; prospective ; C-PEPTIDE ; SERUM ADIPONECTIN ; Adiponectin ; NORTHERN SWEDEN ; GLUCOSE-HOMEOSTASIS ; Glycated haemoglobin
    Abstract: It is hypothesized that insulin resistance and related metabolic factors may influence breast cancer risk, however the epidemiological evidence remains inconclusive. We conducted a case-control study nested in a prospective cohort in Northern Sweden, to clarify the associations of body mass index (BMI), leptin, adiponectin, C-peptide, and glycated haemoglobin (HbA1c) with breast cancer risk. We also investigated whether these associations may be modified by age at diagnosis, tumour stage, and oestrogen and progesterone receptor status. During follow-up, 561 women developed invasive breast cancer and 561 matched controls were selected. Conditional logistic regression was used to calculate odds ratios (OR) as estimates of relative risk, and 95% confidence intervals (CI). The associations of BMI, leptin and HbA1c with breast cancer risk differed significantly according to whether the tumour was diagnosed as stage I or stage II-IV (P (heterogeneity) all 〈 0.05). These factors were significantly inversely associated with risk in the group of stage I tumours, with ORs for top vs. bottom tertile for BMI of 0.48 (95% CI, 0.30-0.78, P (trend) = 0.004); leptin, 0.64 (95% CI, 0.41-1.00, P (trend) = 0.06); and HbA1c, 0.47 (95% CI, 0.28-0.80, P (trend) = 0.005). For stage II-IV tumours, there was a suggestion of an increased risk with higher levels of these factors. There were no significant differences in the associations of BMI, leptin, adiponectin, C-peptide and HbA1c with breast cancer risk in subgroups of age at diagnosis or tumour receptor status. This prospective study suggests that BMI, leptin and HbA1c influence breast tumour initiation and progression
    Type of Publication: Journal article published
    PubMed ID: 18330696
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  • 7
  • 8
    Keywords: CANCER ; BLOOD ; carcinoma ; COHORT ; cohort studies ; cohort study ; RISK ; ASSOCIATION ; HEALTH ; WOMEN ; OBESITY ; PROSPECTIVE COHORT ; COLORECTAL-CANCER ; SWEDEN ; CARCINOMAS ; body mass index ; REGRESSION ; ASSOCIATIONS ; WEIGHT ; BODY-SIZE ; GROWTH-FACTOR-I ; metabolic syndrome ; blood pressure ; SERUM-LEVELS ; prospective ; CORONARY HEART-DISEASE ; INCREASED RISK ; CANCERS ; CANCER-RISK ; CIRCULATING LEVELS ; C-PEPTIDE ; BODY-MASS ; endometrial neoplasms ; journals ; AGED NORWEGIAN MEN ; metabolic syndrome X
    Abstract: The authors examined the association between the metabolic syndrome and risk of incident endometnal and fatal uterine corpus cancer within a large prospective cohort study Approximately 290,000 women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, systolic and diastolic blood pressure, and circulating levels of glucose, total cholesterol, and tnglycendes Relative risks were estimated using Cox proportional hazards regression. The metabolic syndrome was assessed as a composite z score, as the standardized sum of z scores for body mass index, blood pressure, glucose, cholesterol, and tnglycendes. A total of 917 endonnetnal carcinomas and 129 fatal cancers were identified Increased risks of incident endometnal carcinoma and fatal uterine corpus cancer were seen for the metabolic syndrome factors combined, as well as for individual factors (except for cholesterol) The relative risk of endometnal carcinoma for the metabolic syndrome was 1.37 (95% confidence interval 1 28, 1 46) per 1-unit increment of z score The positive associations between metabolic syndrome factors (both individually and combined) and endometrial carcinoma were confined to the heaviest women. The association between the metabolic syndrome and endometnal carcinoma risk seems to go beyond the risk conferred by obesity alone, particularly in women with a high body mass index
    Type of Publication: Journal article published
    PubMed ID: 20219764
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  • 9
    Abstract: BACKGROUND: Circulating levels of insulin-like growth factor I (IGF-I) and its main binding protein, IGF binding protein 3 (IGFBP-3), have been associated with risk of several types of cancer. Heritable factors explain up to 60% of the variation in IGF-I and IGFBP-3 in studies of adult twins. METHODS: We systematically examined common genetic variation in 18 genes in the IGF signaling pathway for associations with circulating levels of IGF-I and IGFBP-3. A total of 302 single nucleotide polymorphisms (SNP) were genotyped in 〉5,500 Caucasian men and 5,500 Caucasian women from the Breast and Prostate Cancer Cohort Consortium. RESULTS: After adjusting for multiple testing, SNPs in the IGF1 and SSTR5 genes were significantly associated with circulating IGF-I (P 〈 2.1 x 10(-4)); SNPs in the IGFBP3 and IGFALS genes were significantly associated with circulating IGFBP-3. Multi-SNP models explained R(2) = 0.62% of the variation in circulating IGF-I and 3.9% of the variation in circulating IGFBP-3. We saw no significant association between these multi-SNP predictors of circulating IGF-I or IGFBP-3 and risk of prostate or breast cancers. CONCLUSION: Common genetic variation in the IGF1 and SSTR5 genes seems to influence circulating IGF-I levels, and variation in IGFBP3 and IGFALS seems to influence circulating IGFBP-3. However, these variants explain only a small percentage of the variation in circulating IGF-I and IGFBP-3 in Caucasian men and women. Impact: Further studies are needed to explore contributions from other genetic factors such as rare variants in these genes and variation outside of these genes.
    Type of Publication: Journal article published
    PubMed ID: 20810604
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  • 10
    Keywords: CANCER ; CELLS ; EXPRESSION ; PATHWAY ; RISK ; GENE ; PROTEIN ; METABOLISM ; GENETIC POLYMORPHISMS ; BREAST-CANCER ; prostate cancer ; PROSTATE-CANCER ; PHENOTYPE ; insulin ; ONCOLOGY ; NUTRITIONAL REGULATION ; GROWTH-FACTOR (IGF)-I ; IGF-BINDING-PROTEINS ; SUPPRESSES ; Fatty acid synthase ; NF-Y ; Susceptibility to cancer
    Abstract: A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk.
    Type of Publication: Journal article published
    PubMed ID: 20965718
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