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  • 1
    Keywords: RECEPTOR ; CANCER ; GROWTH ; GROWTH-FACTOR ; proliferation ; tumor ; CELL-PROLIFERATION ; PATHWAY ; RISK ; GENE ; GENES ; PROTEIN ; TUMORS ; RELEASE ; PATIENT ; BINDING ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; VARIANTS ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; COLORECTAL-CANCER ; PROSTATE-CANCER ; cancer risk ; case-control studies ; SOMATOSTATIN ; CANCER PATIENTS ; nutrition ; FACTOR-I ; BINDING PROTEIN ; SERUM ; SINGLE ; IGF-I ; BINDING-PROTEIN ; case-control study ; ASSOCIATIONS ; RE ; VARIANT ; SINGLE NUCLEOTIDE POLYMORPHISMS ; cell proliferation ; development ; GROWTH-FACTOR-I ; BINDING PROTEIN-3 ; LEVEL ; case control studies ; GENOTYPE DATA ; FACTOR (IGF)-I ; PREMENOPAUSAL WOMEN ; IGFBP3 ; insulin-like growth factor ; PLASMA-LEVELS ; SERUM-LEVELS
    Abstract: Insulin-like growth factor-I (IGF-I) stimulates cell proliferation and can enhance the development of tumors in different organs. Epidemiologic studies have shown that an elevated level of circulating IGF-I is associated to increased risk of breast cancer as well as other cancers. Genetic variants affecting the release or biological action of growth hormone (GH), the main stimulator of IGF-I production, may predict circulating levels of IGF-I and have an effect on cancer risk. We tested this hypothesis with a large case-control study of 807 breast cancer patients and 1,588 matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 22 common single nucleotide polymorphisms in 10 genes involved in GH production and action (GHRH, GHRHR, SST, SSTR1-SSTR5, POU1F1, and GH1), and in parallel, we measured serum levels of IGF-I and IGFBP-3, its major binding protein, in samples of cases and controls. SST and SSTR2 polymorphisms showed weak but statistically significant associations with breast cancer risk. SSTR5 polymorphisms were associated with IGF-I levels, whereas one polymorphism in GHRHR and one in POU1F1 were associated with IGFBP-3 levels. Our conclusion is that common genetic variation in the GH synthesis pathway, as measured by single nucleotide polymorphisms selected in the present study, is not a major determinant of IGF-I and IGFBP-3 circulating levels, and it does not play a major role in altering breast cancer risk
    Type of Publication: Journal article published
    PubMed ID: 16214911
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  • 2
    Keywords: APOPTOSIS ; CANCER ; proliferation ; BLOOD ; CELL ; CELL-PROLIFERATION ; Germany ; MODEL ; MODELS ; COHORT ; RISK ; RISKS ; SITE ; PROTEIN ; PROTEINS ; colon ; BINDING ; ASSOCIATION ; NO ; resistance ; NUMBER ; AGE ; WOMEN ; colorectal cancer ; OBESITY ; COLORECTAL-CANCER ; COUNTRIES ; RATES ; cancer risk ; BINDING-PROTEINS ; DIET ; case-control studies ; DIABETES-MELLITUS ; EPIC ; nutrition ; FACTOR-I ; REGRESSION-MODELS ; physical activity ; BINDING PROTEIN ; insulin ; SERUM ; IGF-I ; ONCOLOGY ; BINDING-PROTEIN ; case-control study ; REGRESSION ; ASSOCIATIONS ; secretion ; BODY-SIZE ; PHYSICAL-ACTIVITY ; LEVEL ; biomarker ; case control studies ; pancreatic ; BLOOD-GLUCOSE ; INSULIN-RESISTANCE ; rectum ; USA ; prospective ; rectal cancer ; prospective study ; CANCERS ; CANCER-RISK ; C-PEPTIDE ; IGFBP-1 ; colorectal ; BINDING PROTEINS ; LOGISTIC-REGRESSION ; IGFBP-2 ; FACTOR BINDING PROTEIN-1 ; IGF ; insulin resistance ; GROWTH-FACTOR (IGF)-I
    Abstract: Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR = 1.56, 95% CI = 1.16-2.09, p(trend) 〈 0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR = 1.37, 95% CI = 1.00-1.88, p(trend) = 0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR 1.67, 95% CI = 1.14-2.46, p(trend) 〈 0.01) than in the rectum (OR 1.42, 95% CI = 0.90-2.25, p(trend) = 0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk. (C) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17372899
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  • 3
    Keywords: CANCER ; GROWTH ; proliferation ; RISK ; GENE ; GENES ; PROTEIN ; PROTEINS ; PATIENT ; BINDING ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; BREAST ; breast cancer ; BREAST-CANCER ; WOMEN ; COLORECTAL-CANCER ; PROSTATE-CANCER ; cancer risk ; FACTOR-I ; SERUM ; IGF-I ; RE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; CANDIDATE GENES ; GROWTH-FACTOR-I ; LEVEL ; case control studies ; single-nucleotide ; GENOTYPE DATA ; FACTOR (IGF)-I ; PREMENOPAUSAL WOMEN ; PLASMA-LEVELS ; SERUM-LEVELS ; ALPHA-5-BETA-1 INTEGRIN ; C-PEPTIDE ; IGFALS ; IGFBP-1 ; IGFBP-3 ; MULTIETHNIC COHORT
    Abstract: Insulin-like growth factor I (IGF-1) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-1 is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-1 carriers may predict circulating levels of IGF-1 and have an impact on cancer risk. We tested this hypothesis with a case - control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-1 and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 50 end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 50 end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians
    Type of Publication: Journal article published
    PubMed ID: 16404426
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