c-peptide and Colorectal-Neoplasms

Independent epidemiological studies have evaluated the association between markers of glucose metabolism (including fasting glucose, fasting insulin, homeostasis model of risk assessment-insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c) and C peptide) and the risk of colorectal cancer (CRC). However, such associations have not been systematically analysed and no clear conclusions have been drawn. Therefore, we addressed this issue using a meta-analysis approach.. Systematic review and meta-analysis.. PubMed and EMBASE were searched up to May 2015.. Either a fixed-effects or random-effects model was adopted to estimate overall ORs for the association between markers of glucose metabolism and the risk of CRC. In addition, dose-response, meta-regression, subgroup and publication bias analyses were conducted.. 35 studies involving 25 566 patients and 5 706 361 participants were included. Higher levels of fasting glucose, fasting insulin, HOMA-IR, HbA1c and C peptide were all significantly associated with increased risk of CRC (fasting glucose, pooled OR=1.12, 95% CI 1.06 to 1.18; fasting insulin, pooled OR=1.42, 95% CI 1.19 to 1.69; HOMA-IR, pooled OR=1.47, 95% CI 1.24 to 1.74; HbA1c, pooled OR=1.22, 95% CI 1.02 to 1.47 (with borderline significance); C peptide, pooled OR=1.27, 95% CI 1.08 to 1.49). Subgroup analysis suggested that a higher HOMA-IR value was significantly associated with CRC risk in all subgroups, including gender, study design and geographic region. For the relative long-term markers, the association was significant for HbA1c in case-control studies, while C peptide was significantly associated with CRC risk in both the male group and colon cancer.. The real-time composite index HOMA-IR is a better indicator for CRC risk than are fasting glucose and fasting insulin. The relative long-term markers, HbA1c and C peptide, are also valid predictors for CRC risk. Considering the included case-control studies in the current analysis, more cohort studies are warranted to enhance future analysis.

Topics: Biomarkers; C-Peptide; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Homeostasis; Humans; Insulin Resistance; Risk Assessment; Risk Factors

Insulin stimulates cell proliferation and inhibits apoptosis. While epidemiologic studies have investigated associations between markers of insulin resistance/hyperinsulinemia (i.e., circulating insulin, homeostasis model assessment-insulin resistance (HOMA-IR), C-peptide) and risk of colorectal adenoma (CRA), the effect size has not yet been quantified.. We aimed to summarize the association between hyperinsulinemia/insulin resistance and risk of CRA, including whether the association is independent of adiposity.. Pubmed and Embase were searched through April, 2015 to identify observational studies investigating the associations between insulin, C-peptide and HOMA-IR and CRA risk. Using the highest versus lowest category meta-analysis and dose-response meta-analysis based on a random-effects model, we estimated summary odds ratio (OR) and the corresponding 95% confidence interval (95% CI).. A total of 27 studies (insulin: 16 studies including 14,007 cases; C-peptide: 11 studies including 8639 cases; HOMA-IR: 8 studies including 11,619 cases) were included in this meta-analysis. The summary ORs of CRA comparing the highest with the lowest quantile were 1.33 for insulin (95% CI=1.12-1.58, I(2)=73.9%, Pheterogeneity<0.001), 1.44 for C-peptide (95% CI=1.13-1.83, I(2)=63.5%, Pheterogeneity=0.003), and 1.33 for HOMA-IR (95% CI=1.10-1.60, I(2)=69.1%, Pheterogeneity=0.004). Upon stratification by ethnicity, higher levels of insulin and C-peptide were significantly associated with increased risk of CRA in non-Asian ethnicity (summary OR for insulin=1.67 [95% CI=1.28-2.17], I(2)=34.9%, Pheterogeneity=0.16; summary OR for C-peptide=1.59 [95% CI=1.22-2.08], I(2)=21.5%, Pheterogeneity=0.27) but not in Asians (summary OR for insulin=1.10 [95% CI=0.92-1.33], I(2)=76.6%, Pheterogeneity=0.001; summary OR for C-peptide=1.27 [95% CI=0.84-1.91], I(2)=72.6, Pheterogeneity=0.01). We observed evidence for the existence of publication bias for insulin (P=0.01 by Egger test) and HOMA-IR (P=0.05 by Egger test). The results were confirmed in linear dose-response meta-analysis. These significant positive associations generally persisted even after adjustment for adiposity, although the effect size was substantially attenuated.. Independent of adiposity, higher levels of insulin, C-peptide, and HOMA-IR were significantly associated with increased risk of CRA. The weaker associations and high heterogeneity in Asian studies warrant further research. These results indicate that insulin resistance and hyperinsulinemia may contribute in part to the association between obesity and CRA risk.

Topics: Adenoma; Adiposity; Blood Glucose; C-Peptide; Colorectal Neoplasms; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Obesity; Risk Factors

Energy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study.. Baseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute-sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS).. Median follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78;. Among patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation.

Topics: Adiponectin; Aged; C-Peptide; Colorectal Neoplasms; Confidence Intervals; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Male; Middle Aged; Neoplasm Proteins; Progression-Free Survival; Proportional Hazards Models; Prospective Studies

Insulin-like growth factor (IGF)-I and IGF-II stimulate neoplastic cell growth and inhibit apoptosis, whereas IGF-binding protein-3 (IGFBP-3) inhibits the bioavailability of IGF-I and has independent proapoptotic activity. We examined the influence of baseline plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide on outcome among patients receiving first-line chemotherapy for metastatic colorectal cancer.. The plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide as well as data on prognostic factors and body size were measured at baseline among 527 patients participating in a randomized trial of first-line chemotherapy for metastatic colorectal cancer.. Higher baseline plasma IGFBP-3 levels were associated with a significantly greater chemotherapy response rate (P = 0.03) after adjusting for other prognostic factors, whereas neither IGF-I nor IGF-II levels significantly predicted tumor response. Higher levels of IGF-I, IGF-II, and IGFBP-3 were all univariately associated with improved overall survival (P = 0.0001 for all). In a model that mutually adjusted for IGF-I and IGFBP-3, as well as other prognostic factors, increasing baseline-circulating IGFBP-3 was associated with a significantly longer time to tumor progression (P = 0.03), whereas circulating IGF-I was not associated with disease progression (P = 0.95). Levels of C-peptide were not associated with any measure of patient outcome.. Among colorectal cancer patients receiving first-line chemotherapy, increasing levels of IGFBP-3, an endogenous antagonist to IGF-I, are associated with an improved objective treatment response and a prolonged time to cancer progression. The IGF pathway may represent an important target for future treatment strategies.

Topics: Biomarkers; Body Mass Index; C-Peptide; Colorectal Neoplasms; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Neoplasm Metastasis

In a randomized clinical trial in 24 patients with colorectal resections the different behaviour of glucose tolerance (GT) in the early post-operative period was investigated. Especially, we were concerned with the way nutritional substrate were applicated. Therefore 2 groups were randomly formed for a six day period of enteral versus parenteral nutrition. To check the GT enteral tolerance-tests were done preoperatively, and on day 1, 3 and 6 postoperatively. Our results show a significant improvement of GT in the enteral group on 3, and 6, postoperative days, as well as a significantly higher insulin secretion on 3, postoperative day. C-Peptide displays similar high concentrations as a sign of elevated insulin secretion. These results prove, that enteral glucose application is superior to the parenteral way in early postoperative nutrition.

Topics: C-Peptide; Colorectal Neoplasms; Enteral Nutrition; Glucose Solution, Hypertonic; Glucose Tolerance Test; Humans; Infusion Pumps; Insulin; Parenteral Nutrition, Total; Postoperative Care

There are limited studies investigating the role of irisin in colorectal cancer, and the results are diverse. The role of irisin in colorectal cancer patients was investigated in this study.. This cross-sectional study included 53 patients diagnosed with colorectal cancer (CRC) and 87 healthy volunteers. Serum irisin, glucose, insulin, C-peptide, and whole blood hemoglobin A1c (HbA1c) levels were measured in venous blood samples taken from patients and the control group.. The mean serum irisin levels were significantly lower in the patient group (23.97 ± 16.94 ng/mL) than in the control group (32.71 ± 17.26 ng/mL) (p = 0.004). Serum glucose levels were 96.58 ± 15.12 mg/dL in the patient group and 81.91 ± 11.24 mg/dL in the control group. Serum glucose levels were significantly higher in the patient group than in the control group (p < 0.01). In the patient group, there was no statistically significant difference between metastasis (+) patients and metastasis (-) patients in terms of serum irisin levels (27.53 ± 18.48 ng/mL and 21.23 ± 15.43 ng/mL, respectively; p = 0.182).. Our study has provided new insights into the potential role of irisin in CRC. However, further studies, including in vitro, in vivo, and larger patient groups, are necessary to fully understand the potential of irisin as a biomarker or therapeutic target for CRC and other diseases.

Topics: C-Peptide; Colorectal Neoplasms; Cross-Sectional Studies; Fibronectins; Glucose; Humans

Observational studies suggest that abnormal glucose metabolism and insulin resistance contribute to colorectal cancer; however, the causal association remains unknown, particularly in Asian populations. A two-sample Mendelian randomisation analysis was performed to determine the causal association between genetic variants associated with elevated fasting glucose, haemoglobin A1c (HbA1c), and fasting C-peptide and colorectal cancer risk. In the single nucleotide polymorphism (SNP)-exposure analysis, we meta-analysed study-level genome-wide associations of fasting glucose (~ 17,289 individuals), HbA1c (~ 52,802 individuals), and fasting C-peptide (1,666 individuals) levels from the Japanese Consortium of Genetic Epidemiology studies. The odds ratios of colorectal cancer were 1.01 (95% confidence interval [CI], 0.99-1.04, P = 0.34) for fasting glucose (per 1 mg/dL increment), 1.02 (95% CI, 0.60-1.73, P = 0.95) for HbA1c (per 1% increment), and 1.47 (95% CI, 0.97-2.24, P = 0.06) for fasting C-peptide (per 1 log increment). Sensitivity analyses, including Mendelian randomisation-Egger and weighted-median approaches, revealed no significant association between glycaemic characteristics and colorectal cancer (P > 0.20). In this study, genetically predicted glycaemic characteristics were not significantly related to colorectal cancer risk. The potential association between insulin resistance and colorectal cancer should be validated in further studies.

Topics: Blood Glucose; C-Peptide; Colorectal Neoplasms; Diabetes Mellitus, Type 2; East Asian People; Genome-Wide Association Study; Glucose; Glycated Hemoglobin; Humans; Insulin Resistance; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors

Self-reported type 2 diabetes mellitus (T2DM) is a risk factor for many cancers, suggesting its pathology relates to carcinogenesis. We conducted a case-cohort study to examine associations of hemoglobin A

Topics: C-Peptide; Cohort Studies; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Hemoglobin A; Humans; Liver Neoplasms; Male

Energy balance-related factors, such as body mass index (BMI), diet, and physical activity, may influence colorectal cancer etiology through interconnected metabolic pathways, but their combined influence is less clear.. We used reduced rank regression to derive three energy balance scores that associate lifestyle factors with combinations of prediagnostic, circulating levels of high-sensitivity C-reactive protein (hsCRP), C-peptide, and hemoglobin A. The derived scores comprised BMI, physical activity, screen time, and 14 food groups, and explained 5.1% to 10.5% of the variation in biomarkers. The HR and 95% confidence interval (CI) for quartile 4 versus 1 of the HbA. These results further support hypotheses that systemic biomarkers of metabolic health-inflammation and abnormal glucose homeostasis-mediate part of the relationship between several energy balance-related modifiable factors and colorectal cancer risk.. Results support cancer prevention guidelines for maintaining a healthful body weight, consuming a healthful diet, and being physically active. More research is needed on these clusters of exposures with molecular phenotypes of tumors.

Topics: Aged; Biomarkers; Body Mass Index; C-Peptide; Colorectal Neoplasms; Energy Metabolism; Exercise; Feeding Behavior; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hyperinsulinism; Incidence; Inflammation; Male; Middle Aged; Prospective Studies; Receptors, Immunologic; Risk Assessment

Topics: Adiponectin; Adult; Aged; Biomarkers; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Insulin; Leptin; Longitudinal Studies; Male; Microsatellite Instability; Middle Aged; Mutation; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Risk Factors

Insulin response may be important in colorectal cancer development. Diet modulates insulin response and may be a modifiable factor in colorectal cancer prevention.. We examined associations between hyperinsulinemic diets and colorectal cancer risk with the use of an empirical dietary index for hyperinsulinemia (EDIH), a food-based index that characterizes dietary insulinemic potential on the basis of circulating C-peptide concentrations.. Diet was assessed every 4 y with food-frequency questionnaires in 46,210 men (Health Professionals Follow-Up Study, 1986-2012) and 74,191 women (Nurses' Health Study, 1984-2012) to calculate EDIH scores. Multivariable-adjusted Cox regression was used to calculate HRs and 95% CIs for colorectal, proximal/distal colon, and rectal cancer risk.. During 26 y of follow-up, we documented 2683 incident colorectal cancer cases. Comparing participants in the highest with those in the lowest quintiles, higher EDIH scores were associated with 33% (men: HR: 1.33; 95% CI: 1.11, 1.61; P-trend = 0.0005), 22% (women: HR: 1.22; 95% CI: 1.03, 1.45; P-trend = 0.01), and 26% (men and women: pooled HR: 1.26; 95% CI: 1.12, 1.42; P-trend <0.0001) higher risk of developing colorectal cancer. The positive associations were limited to the distal colon and rectum in men and to the distal and proximal colon in women; however, combined risk estimates were significant for all anatomic locations except for the rectum. For example, comparing participants in extreme EDIH quintiles, there was no significant association for proximal colon cancer in men (HR: 1.15; 95% CI: 0.84, 1.57; P-trend = 0.32), but the risk was elevated for distal colon (HR: 1.63; 95% CI: 1.14, 2.32; P-trend = 0.002) and rectal (HR: 1.63; 95% CI: 1.09, 2.44; P-trend = 0.01) cancer. Among women, the risk was elevated for proximal (HR: 1.28; 95% CI: 1.00, 1.63; P-trend = 0.03) and distal (HR: 1.46; 95% CI: 1.05, 2.03; P-trend = 0.03) colon cancer but not for rectal cancer (HR: 0.88; 95% CI: 0.60, 1.29; P-trend = 0.61).. The findings suggest that the insulinemic potential of diet may partly underlie the influence of dietary intake on colorectal cancer development. This observational study was registered at www.clinicaltrials.gov as NCT03364582.

Topics: Aged; C-Peptide; Colorectal Neoplasms; Diet; Female; Humans; Insulin; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Risk

Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.. The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of. These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Topics: Adiposity; Biomarkers; Body Mass Index; Body Size; C-Peptide; Case-Control Studies; Chi-Square Distribution; Colorectal Neoplasms; Europe; Female; Health Status; Humans; Hyperinsulinism; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Obesity; Obesity, Metabolically Benign; Odds Ratio; Phenotype; Prospective Studies; Protective Factors; Risk Assessment; Risk Factors; Waist Circumference

Obesity is a recognised positive risk factor for colorectal adenoma and colorectal cancer. Obesity is associated with insulin resistance and compensatory hyperinsulinaemia, and circulating insulin and C-peptide, a biomarker of insulin levels, have been positively associated with colorectal cancer risk. However, whether a similar relationship exists for colorectal adenomas, an established colorectal cancer precursor, is unclear.. In a nested case-control study of 273 colorectal adenoma cases and 355 matched controls from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, serum C-peptide levels were measured by a chemiluminescent immunometric assay. Multivariable unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for colorectal adenoma within quartiles of C-peptide. Further, to explore the temporal stability of C-peptide, repeat samples from the incident adenoma cases (n=50) and controls (n=30), over a 5-year period were assayed and the intra-class correlations (ICC) estimated.. In a multivariable model that included established colorectal adenoma risk factors, C-peptide levels were not associated with colorectal adenoma (Q4 vs. Q1, OR 0.83, 95% CI: 0.52-1.31; P-trend 0.32); similar null associations were observed by gender, by adenoma subsite and for advanced adenomas. Among control participants, the ICC value over a 5-year period was 0.66.. Our results suggest that higher C-peptide levels were not associated with colorectal adenoma incidence in this study population. Other biological pathways associated with obesity may be more relevant to the early stages of colorectal tumorigenesis.

Topics: Adenoma; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Incidence; Male; Middle Aged; Obesity; Prospective Studies; Risk Factors

Insulin-like growth factor peptides play important roles in regulating cell growth, cell differentiation, and apoptosis, and have been demonstrated to promote the development of colorectal cancer (CRC).. To examine the association of insulin-related biomarkers including insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and C-peptide with CRC risk and assess their relevance in predictive models.. The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3 and C-peptide were estimated using unconditional logistic regression models in 100 colorectal cancer cases and 100 control subjects. Areas under the receiving curve (AUC) and integrated discrimination improvement (IDI) statistics were used to assess the discriminatory potential of the models.. Serum levels of IGF-1 and IGFBP-3 were negatively associated with colorectal cancer risk (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01, OR=0.06, 95%CI: 0.03-0.15, P for trend <.01 respectively) and serum C-peptide was positively associated with risk of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to the risk model, prediction for the risk of colorectal cancer had substantially improved when all selected biomarkers IGF-1, IGFBP-3 and inverse value of C-peptide were simultaneously included inthe reference model [P for AUC improvement was 0.02 and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)].. The results provide evidence for an association of insulin-related biomarkers with colorectal cancer risk and point to consideration as candidate predictor markers.

Topics: Aged; Area Under Curve; Biomarkers, Tumor; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Middle Aged; Neoplasm Staging; Odds Ratio; Prognosis; Risk Factors; Survival Rate

Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location.. In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma.. Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00-1.16; P = .04) for fasting glucose, 1.07 (0.99-1.15; P = .10) for insulin, 1.09 (1.02-1.18, P = .02) for HOMA, 1.09 (1.01-1.17; P = .02) for hemoglobin A1c, and 1.14 (1.05-1.24; P = .002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99-1.25; P = .08), 1.10 (0.98-1.24; P = .12), 1.15 (1.02-1.29; P = .02), 1.14 (1.01-1.28; P = .03), and 1.20 (1.05-1.37; P = .007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94-1.84; P = .11), 1.23 (0.87-1.75; P = .24), 1.30 (0.92-1.85; P = .14), 1.13 (0.79-1.61; P = .50), and 1.67 (1.15-2.42; P = .007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13-1.24; P < .001), nonadvanced adenoma (aPR, 1.30; 95% CI, 1.20-1.40; P < .001), and advanced adenoma (aPR, 1.42; 95% CI, 1.14-1.78; P = .002). Associations were similar for adenomas located in the distal versus proximal colon.. Increasing levels of glucose, HOMA values, levels of hemoglobin A1c and C-peptide, and metabolic syndrome are significantly associated with the prevalence of adenomas. Adenomas should be added to the list of consequences of altered glucose metabolism.

Topics: Adenoma; Adult; Biomarkers; Blood Glucose; C-Peptide; Colorectal Neoplasms; Cross-Sectional Studies; Diabetes Complications; Female; Glucose; Glycated Hemoglobin; Humans; Insulin; Male; Metabolic Syndrome; Middle Aged; Regression Analysis; Retrospective Studies; Risk Factors

Dysregulated insulin signaling is thought to contribute to cancer risk.. To determine if insulin-related serum factors are associated with colon polyps, 126 asymptomatic men (48-65 years) were recruited at colonoscopy. Blood was collected. Odds ratios were determined using polytomous logistic regression for polyp number and type.. Males with serum C-peptide concentration >3.3 ng/mL were 3.8 times more likely to have an adenoma relative to no polyp than those with C-peptide ≤1.8 ng/mL. As C-peptide tertile increased, an individual was 2 times more likely to have an adenoma (P = 0.01) than no polyp. There were no associations between insulin-like growth factor or its binding proteins with polyp number or type. Males with soluble receptor for advanced glycation end products (sRAGE) concentration >120.4 pg/mL were 0.25 times less likely to have ≥3 polyps relative to no polyps compared with males with sRAGE ≤94.5 pg/mL. For each increase in sRAGE tertile, a man was 0.5 times less likely to have ≥3 polyps than no polyps (P = 0.03). Compared with males with a serum vascular endothelial growth factor (VEGF) concentration ≤104.7 pg/mL, males with a serum VEGF concentration >184.2 pg/mL were 3.4 times more likely to have ≥3 polyps relative to no polyps. As the VEGF tertile increased, a man was 1.9 times more likely to have ≥3 polyps than no polyps (P = 0.049).. Serum concentrations of C-peptide, sRAGE, and VEGF may indicate which men could benefit most from colonoscopy.. Identification of biomarkers could reduce medical costs through the elimination of colonoscopies on low-risk individuals.

Topics: Adenoma; Aged; C-Peptide; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Glycation End Products, Advanced; Humans; Insulin; Logistic Models; Male; Middle Aged; Somatomedins; Vascular Endothelial Growth Factor A

The aim of the study was to analyse the prevalence and characteristics of secondary diabetes induced by 5-fluorouracil (5-FU) based chemotherapy in non-diabetic patients with colorectal cancer (CRC).. A total of 422 consecutive CRC patients who received 5-FU-based chemotherapy were retrospectively analysed. Fasting plasma glucose (FPG) levels were determined before each cycle of chemotherapy during active treatment and regular follow-up. The prevalence and characteristics of secondary hyperglycaemia were investigated, with special focus on the clinical outcome.. Among the 422 CRC patients, 60 had pre-existing hyperglycaemia. In the remaining 362 with normal FPG levels before chemotherapy, 42 (11.6%) and 41 (11.3%) patients developed diabetes and impaired fasting glucose during the study period. Among the 42 secondary diabetic patients, 22 (52.4%) received anti-diabetes drug therapy, in 7 (16.7%) cases the FPG level returned to normal without any active intervention, and 13 (30.9%) cases received diet control and physiotherapy. Thirty-one (8.6%) patients developed diabetes. Based on the Common Terminology Criteria for Adverse Events, an adverse event over Grade 3 occurred in seven cases during follow-up. Diabetes-related adverse events had a serious negative impact on chemotherapy in six cases. Diabetes-related death occurred in three patients.. Secondary diabetes associated with 5-FU-based chemotherapy occurs in around 10% of CRC patients, with a significant negative impact on treatment and clinical outcome. 5-FU-related diabetes should be regarded as a common side effect of 5-FU treatment.

Topics: Aged; Analysis of Variance; Antimetabolites, Antineoplastic; C-Peptide; Colorectal Neoplasms; Diabetes Mellitus; Feeding Behavior; Female; Fluorouracil; Glucose Tolerance Test; Humans; Hyperglycemia; Hypoglycemic Agents; Male; Middle Aged; Physical Therapy Modalities; Retrospective Studies; Statistics, Nonparametric; Treatment Outcome

There is observational and clinical evidence that indicates that sex hormones affect development of colorectal cancer in men and women. However, the relationship between endogenous sex hormone levels and colorectal cancer is unclear.. We collected data on lifestyle, medical history, and diet (through 2008), along with blood samples, from the Nurses' Health Study, the Women's Health Study, the Health Professional Follow-up Study, and the Physicians' Health Study II. We measured plasma levels of estrone, estradiol, testosterone, sex hormone binding globulin (SHBG), and C-peptide among 730 women (293 cases of colorectal cancer and 437 healthy individuals as controls) and 1158 men (439 colorectal cancer cases and 719 controls) and used unconditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals. All statistical tests were 2-sided.. Total testosterone, SHBG, and the ratio of estradiol to testosterone were associated with colorectal cancer in men after adjustments for matching and risk factors for colorectal cancer, including body mass index and plasma levels of C-peptide. The RRs in the highest relative to the lowest quartile were 0.62 for testosterone (95% confidence interval, 0.40-0.96), 0.65 for SHBG (95% confidence interval, 0.42-0.99), and 2.63 for the ratio (95% confidence interval, 1.58-4.36) (P values for trend ≤ .02). However, in women, only the ratio of estradiol to testosterone was (inversely) associated with colorectal cancer after adjustments for all factors (RR, 0.43; 95% confidence interval, 0.22-0.84; P value for trend = .03).. On the basis of combined data from 4 population studies, there appears to be an association between levels of sex hormones and colorectal cancer risk in men. There also appears to be an inverse association between the ratio of estradiol to testosterone and colorectal cancer in postmenopausal women.

Topics: Aged; C-Peptide; Colorectal Neoplasms; Female; Gonadal Steroid Hormones; Humans; Male; Middle Aged; Risk Assessment; Sex Hormone-Binding Globulin

Although numerous studies have assessed the effect of foods and nutrients on colorectal carcinogenesis, few studies have investigated human eating behavior in relation to risk of colorectal cancer. In our study, we assessed whether the reported behavior of eating anything at anytime influenced colorectal cancer risk and related plasma biomarkers. We prospectively followed up 55,540 women in the Nurses' Health Study who were aged 48-73 years, had no history of cancer, ulcerative colitis or diabetes and responded to the item "I eat anything I want, anytime I want" in the 1994 questionnaire. We also analyzed blood samples for 1,994 women, which were collected in 1989-1990. During 12 years of follow-up, 552 colorectal cancer cases were documented. After adjusting for age, smoking, body mass index, physical activity, red and processed meat and other known risk factors for colorectal cancer, women who reported eating anything at anytime experienced an increased risk of colorectal cancer (relative risk = 1.28, 95% confidence interval = 1.06-1.56) compared to those who did not report this behavior. In addition, reporting eating anything at anytime was associated with higher fasting plasma levels of insulin (p = 0.04) and C-peptide (p = 0.05). In conclusion, reports of eating anything at anytime are associated with an increased risk of colorectal cancer in this large prospective cohort study, independent of other potential risk factors for colorectal cancer.

Topics: Adult; Aged; Biomarkers, Tumor; Body Mass Index; C-Peptide; Cohort Studies; Colorectal Neoplasms; Cross-Sectional Studies; Feeding Behavior; Female; Follow-Up Studies; Humans; Insulin; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Smoking; Surveys and Questionnaires; United States

Accumulating evidence has implicated insulin and the insulin-like growth factor (IGF) axis in colorectal carcinogenesis. Of interest, adiposity is likely to impose a greater risk on men than on women, which indicates that the association of insulin and the IGF axis with colorectal neoplasia may differ by gender. However, epidemiological evidence for this possible gender difference is limited to date.. We measured plasma concentrations of C-peptide, IGF-I and IGF-binding proteins (IGFBPs) 1 and 3 in 1520 healthy volunteer examinees who underwent total colonoscopy between February 2004 and February 2005, and cross-sectionally investigated the association of these biomarkers with colorectal adenoma by gender. An unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for colorectal adenoma after adjustment for potential confounders.. We observed a positive association of C-peptide and IGF-I (P (trend)<0.001 and 0.02, respectively) and an inverse association of IGFBP-1 (P (trend)=0.002) with colorectal adenoma in men. Adjusted ORs of colorectal adenoma for the highest compared with the lowest quartile were also statistically significant for C-peptide (OR: 2.62, 95% CI: 1.71-4.01), IGF-I (OR: 1.63, 95% CI: 1.08-2.46) and IGFBP-1 (OR: 0.49, 95% CI: 0.32-0.75). In contrast, no measurable association was seen in women. Corresponding ORs for C-peptide, IGF-I and IGFBP-1 were 0.98 (95% CI: 0.56-1.71), 0.79 (95% CI: 0.44-1.43) and 1.05 (95% CI: 0.60-1.86), respectively. The gender difference was statistically significant for C-peptide (P (interaction)=0.03) and marginally significant for IGF-I and IGFBP-1 (P (interaction)=0.14 and 0.12, respectively).. Our observations suggest that insulin and the IGF axis act differently by gender in colorectal carcinogenesis, at least in its early stage. The findings of this study further our understanding of the complexities of the gender difference in the association between adiposity and colorectal neoplasia.

Topics: Adenoma; Adult; Aged; Asian People; C-Peptide; Case-Control Studies; Cell Transformation, Neoplastic; Colonoscopy; Colorectal Neoplasms; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Life Style; Logistic Models; Male; Middle Aged; Obesity; Odds Ratio; Risk Factors; Sex Distribution; Sex Factors; Surveys and Questionnaires

Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive.. We tested magnesium-colorectal cancer hypothesis in the Nurses' Health Study, in which 85 924 women free of cancer in 1980 were followed until June 2008. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95% confidence intervals).. In the age-adjusted model, magnesium intake was significantly inversely associated with colorectal cancer risk; the RRs from lowest to highest decile of total magnesium intake were 1.0 (ref), 0.93, 0.81, 0.72, 0.74, 0.77, 0.72, 0.75, 0.80, and 0.67 (P(trend)<0.001). However, in the MV model adjusted for known dietary and non-dietary risk factors for colorectal cancer, the association was significantly attenuated; the MV RRs were 1.0 (ref), 0.96, 0.85, 0.78, 0.82, 0.86, 0.84, 0.91, 1.02, and 0.93 (P(trend)=0.77). Similarly, magnesium intakes were significantly inversely associated with concentrations of plasma C-peptide in age-adjusted model (P(trend)=0.002) but not in multivariate-adjusted model (P(trend)=0.61). Results did not differ by subsite or modified by calcium intakes or body mass index.. These prospective results do not support an independent association of magnesium intake with either colorectal cancer risk or plasma C-peptide levels in women.

Topics: Body Mass Index; C-Peptide; Calcium; Colorectal Neoplasms; Diet; Female; Follow-Up Studies; Humans; Incidence; Insulin; Insulin Secretion; Magnesium; Middle Aged; Prospective Studies; Risk Factors; United States

Higher serum C-peptide concentrations have shown to be associated with an increased risk of colorectal cancer (CRC). Therefore, we used diet information to identify food groups that correlated with fasting serum concentrations of C-peptide and assess the association of this dietary pattern and CRC risk.. Major food contributors to fasting C-peptide concentrations were identified with stepwise linear regression in a subsample (n = 833) of women from a large cohort. We then summed the consumption frequency of the major food contributors to form a C-peptide dietary pattern for the entire cohort (n = 66,714). Risk for CRC was computed using Cox proportional hazard model with the C-peptide dietary pattern score as the predictor.. In up to 20 years of follow-up, we ascertained 985 cases of CRC and 758 colon cancer. After adjusting for confounders, the C-peptide dietary pattern, characterized by higher meat, fish, and sweetened beverage intake, but lower coffee, high fat dairy, and whole grains intake, showed direct association with CRC risk (RR comparing extreme quintiles = 1.29, 95 % CI = 1.05-1.58, p trend = 0.048). The same comparison was slightly stronger for colon cancer (RR = 1.35, 95 % CI = 1.07-1.70, p trend = 0.009). In stratified analysis, there was no association between the C-peptide dietary pattern and colon cancer among lean and active women. However, for overweight or sedentary women, RR for the same comparison was 1.58 (95 % CI = 1.20-2.07, p trend = 0.002) (p for interaction = 0.007).. We derived a dietary pattern that correlated with C-peptide concentrations. This pattern was associated with an increase in colon cancer, especially among women who were overweight or sedentary.

Topics: Beverages; C-Peptide; Cohort Studies; Colorectal Neoplasms; Diet; Diet, High-Fat; Edible Grain; Feeding Behavior; Female; Follow-Up Studies; Humans; Meat; Middle Aged; Overweight; Proportional Hazards Models; Risk Factors; Sedentary Behavior

Lower concentrations of the insulin-like growth factor binding protein-1 (IGFBP-1) and elevated concentrations of insulin or C-peptide have been associated with an increase in colorectal cancer risk (CRC). However few studies have evaluated IGFBP-1 and C-peptide in relation to adenomatous polyps, the only known precursor for CRC.. Between November 2001 and December 2002, we examined associations between circulating concentrations of insulin, C-peptide, IGFBP-1 and apoptosis among 190 individuals with one or more adenomatous polyps and 488 with no adenomatous polyps using logistic regression models.. Individuals with the highest concentrations of C-peptide were more likely to have adenomas (OR = 2.2, 95% CI 1.4-4.0) than those with the lowest concentrations; associations that appeared to be stronger in men (OR = 4.4, 95% CI 1.7-10.9) than women. Individuals with high insulin concentrations also had a higher risk of adenomas (OR = 3.5, 95% CI 1.7-7.4), whereas higher levels of IGFBP-1 were associated with a reduced risk of adenomas in men only (OR = 0.3, 95% CI 0.1-0.7). Overweight and obese individuals with higher C-peptide levels (>1(st) Q) were at increased risk for lower apoptosis index (OR = 2.5, 95% CI 0.9-7.1), an association that remained strong in overweight and obese men (OR = 6.3, 95% CI 1.0-36.7). Higher levels of IGFBP-1 in overweight and obese individuals were associated with a reduced risk of low apoptosis (OR = 0.3, 95% CI 0.1-1.0).. Associations between these peptides and the apoptosis index in overweight and obese individuals, suggest that the mechanism by which C-peptide could induce adenomas may include its anti-apoptotic properties. This study suggests that hyperinsulinemia and IGF hormones predict adenoma risk, and that outcomes associated with colorectal carcinogenesis maybe modified by gender.

Topics: Adenoma; Adult; Aged; Apoptosis; Body Mass Index; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Intestinal Mucosa; Male; Middle Aged; Odds Ratio; Risk

This study investigated the relationship of obesity, insulin resistance, inflammation and angiogenesis with cancer progression and survival in a colorectal cancer cohort.. Clinical and pathological data, along with anthropometric and follow-up data, were collected from 344 consecutive colorectal cancer patients. Serum samples at diagnosis were analysed by immunoassay for adiponectin, C-reactive protein (CRP), vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang-2), insulin-like growth factor-1 (IGF-1), insulin and C-peptide.. Serum Ang-2 and VEGF-A levels increased with tumour T stage (P=0.007 and P=0.025, respectively) and N stage (P=0.02 and P=0.03, respectively), and correlated with CRP levels (r=0.43, P<0.001 and r=0.23, P<0.001, respectively). Angiopoietin-2 correlated with C-peptide (r=0.14, P=0.007) and VEGF-A with IGF-1 in males (r=0.25, P=0.001). Kaplan-Meier analysis showed that patients with high serum levels of CRP and Ang-2 had significantly reduced survival (both P≤0.001). After adjusting for tumour stage and age, Ang-2 remained a significant predictor of survival. The CRP levels were inversely associated with survival in American Joint Committee on Cancer stage II patients (P=0.038), suggesting that CRP could be used to support treatment decisions in this subgroup. Serum markers and anthropometric measures of obesity correlated with each other, but not with survival.. Our study supports the concept that obesity-related inflammation, rather than obesity itself, is associated with colorectal cancer progression and survival. The study confirms serum Ang-2 as a predictive marker for outcome of colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Angiopoietin-2; Biomarkers; Body Mass Index; C-Peptide; C-Reactive Protein; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Male; Middle Aged; Obesity; Prospective Studies; Survival Rate; Treatment Outcome; Vascular Endothelial Growth Factor A

Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide have been implicated in colorectal carcinogenesis. However, in contrast to vitamin D IGF-1 is not an easily modifiable risk factor.. Combining data from the Health Professionals Follow up Study (HPFS) and the Nurses' Health Study cohort (NHS) additive and multiplicative interactions were examined between plasma 25-hydroxyvitamin D (25(OH)D) and IGF-1, IGFBP-3 as well as C-peptide levels in 499 cases and 992 matched controls. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively.. Compared to participants with high 25(OH)D and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF-1/IGFBP-3 ratio were at elevated risk of colorectal cancer when 25(OH)D was low (odds ratio (OR): 2.05 (95% CI: 1.43 to 2.92), but not when 25(OH)D was high (OR:1.20 (95% CI: 0.84 to 1.71, p(interaction): additive =0.06, multiplicative =0.25). Similarly, compared to participants with high 25(OH)D and low molar IGF-1/IGFBP-3 ratio and low C-peptide levels (reference group), participants with a combination of either high IGF-1/IGFBP-3 ratio or high C-peptide were at elevated risk for colorectal cancer when 25(OH)D was low (OR =1.90, 95% CI: 1.22 to 2.94) but not when 25(OH)D was high (OR=1.15, 95% CI: 0.74 to 1.77, p(interaction): additive=0.004; multiplicative=0.04).. The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP-3 ratio or C-peptide levels.

Topics: Adult; Aged; C-Peptide; Colorectal Neoplasms; Female; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Risk Factors; Surveys and Questionnaires; Vitamin D

Adipocytokines are adipocyte-secreted hormones associated with some malignancies such as colorectal, breast, and prostate cancer. We hypothesized that changes in the levels of adipocytokines may indicate the carcinogenesis and progression of colorectal cancer and adenoma, and investigated the association of the blood levels of several adipocytokines through a case-control study. Blood levels of adiponectin, leptin, resistin, visfatin, and C-peptide at diagnosis were measured in 115 colorectal cancer patients and 115 age-, sex-, and body mass index-matched controls. The same analysis was performed in 72 colorectal adenoma patients and 72 controls. Logistic regression models were used for estimating odds ratios and 95% confidence intervals, and one-way anova was performed to determine the prevalence of each variable between two or more groups. Resistin and visfatin levels in cancer patients were significantly higher than those of controls on multivariate analysis (P = 0.03 and P < 0.01, respectively). Stage progression significantly correlated with resistin and visfatin levels (P < 0.01 for both). The adiponectin level in adenoma patients was significantly lower than that of controls on multivariate analysis (P = 0.04). Its level was inversely correlated with the number of adenoma (P = 0.02), but not correlated with the size of adenoma. Resistin and visfatin may be good biomarkers of colorectal malignant potential and stage progression. Adiponectin level may be a good biomarker of colorectal adenoma.

Topics: Adenoma; Adipokines; Adiponectin; Adult; Aged; Biomarkers, Tumor; Body Mass Index; C-Peptide; Colorectal Neoplasms; Cytokines; Female; Humans; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Resistin

Circulating levels of insulin and insulin-like growth factor (IGF) hormones have been associated with colorectal cancer risk, but few studies have examined their associations with colorectal adenoma.. We measured plasma C-peptide, a marker of insulin secretion, and IGF hormones in a case-control study of 554 pathologically confirmed, first-time adenoma cases and 786 controls with normal endoscopy among Caucasians, Japanese, and Native Hawaiians in Hawaii.. High plasma levels of C-peptide were statistically significantly associated with risk of colorectal adenoma [multivariate odds ratio (95% confidence interval) for increasing quartiles: 1.0, 0.91 (0.65-1.27), 1.21 (0.86-1.71), and 1.79 (1.23-2.60); P(trend) = 0.0002]. We also observed a statistically significant inverse association between levels of plasma IGF binding protein-1 (IGFBP-1) and adenoma risk [1.0, 0.97 (0.70-1.34), 0.82 (0.58-1.15), and 0.47 (0.32-0.70); P(trend) <0.0001]. These associations remain significant after adjusting for each other and were not confounded by known risk factors. IGF-I, IGFBP-3, body mass index, and waist or hip circumference were not independently associated with adenoma risk.. These results provide evidence for an association of insulin and IGFBP-1 levels with colorectal adenoma.. This study suggests that hyperinsulinemia and IGF hormones may act as etiologic factors in colorectal carcinogenesis, as early as during adenoma formation.

Topics: Adenoma; Aged; Asian People; Body Mass Index; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Ethnicity; Female; Hawaii; Humans; Hyperinsulinism; Insulin-Like Growth Factor Binding Protein 1; Japan; Male; Middle Aged; Risk Factors; White People

Serum adiponectin, leptin, C-peptide, and homocysteine are indicators for obesity, hyperinsulinemia, and chronic inflammation, which have all been associated with colorectal cancer.. To determine whether serum adiponectin, leptin, C-peptide, and homocysteine are associated with fat, fiber, fruit and vegetable, flavonol, or dry bean intake and colorectal adenoma recurrence.. Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (95% CI) for adenoma recurrence in 627 participants from the control arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence.. Serum concentrations of C-peptide and homocysteine were inversely related to fiber, fruit and vegetable, and flavonol intake and positively related to percentage of calories from fat (all P(trend) < or = 0.01). High homocysteine concentrations were associated with any (4th versus 1st quartile: OR, 2.26; 95% CI, 1.30-3.94) and more than one adenoma recurrence (OR, 2.11; 95% CI, 1.01-4.40). Individuals in the highest, versus lowest, tertile of serum leptin concentration had a decreased risk of advanced adenoma recurrence (OR, 0.22; 95% CI, 0.06-0.79).. Our results suggest that serum homocysteine may serve as an indicator of dietary exposure, including a low-fat and high-fiber, high-fruit and vegetable, and high-flavonol diet, as well as colorectal adenoma recurrence.. Discovering biomarkers that are both modifiable and can predict cancer risk is critical. We identified serum homocysteine as a novel indicator that is modified by diet and predicts risk of adenoma recurrence.

Topics: Adenoma; Adiponectin; Adult; Aged; Aged, 80 and over; C-Peptide; Colorectal Neoplasms; Diet; Female; Follow-Up Studies; Homocysteine; Humans; Leptin; Male; Middle Aged; Neoplasm Recurrence, Local; Recurrence; Risk Factors

Obesity, sedentary lifestyle, and Western dietary pattern have been linked to increased risk of cancer recurrence and mortality among patients with surgically resected colorectal cancer. Excess energy balance leads to increased circulating insulin and depressed levels of circulating insulin-like growth factor binding protein (IGFBP) -1, which promote cancer cell growth in preclinical models.. Among 373 patients diagnosed with nonmetastatic colorectal cancer between 1991 and 2004, we performed a prospective observational study nested within two large US cohorts to evaluate the association between mortality and prediagnosis circulating C-peptide (a marker of insulin secretion), IGFBP-1, insulin-like growth factor-I (IGF-I), and IGFBP-3.. Compared with patients in the bottom quartile, patients in the top quartile of plasma C-peptide had an age-adjusted hazard ratio (HR) for death of 1.87 (95% CI, 1.04 to 3.36; P = .03 for trend), whereas those in the top quartile of circulating IGFBP-1 had a significant reduction in mortality (HR = 0.48; 95% CI, 0.28 to 0.84; P = .02 for trend). Little change in these estimates was noted after adjusting for other covariates known or suspected to influence survival. No associations were noted between mortality and IGF-I or IGFBP-3, which are two components of the IGF axis not closely correlated with lifestyle factors.. Among patients with surgically resected colorectal cancer, higher levels of prediagnosis plasma C-peptide and lower levels of prediagnosis plasma IGFBP-1 were associated with increased mortality. Circulating insulin and IGFBP-1 are potential mediators of the association between lifestyle factors and mortality after colorectal cancer resection.

Topics: Adult; Aged; C-Peptide; Cohort Studies; Colorectal Neoplasms; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Middle Aged; Neoplasm Staging; Somatomedins

To examine the relation of well-known factors of the metabolic syndrome (MetS) as well as related circulating factors, with risk of colorectal cancer.. We performed a case control study of 306 colorectal cancer cases and 595 matched controls nested in the Northern Sweden Health and Disease Cohort. Levels of C-peptide, glycated haemoglobin (HbA1c), leptin and adiponectin were measured in cryopreserved samples. Body mass index (BMI), systolic and diastolic blood pressure and fasting and post-load plasma glucose, had been measured in a subcohort. Conditional logistic regression was used to calculate odds ratios (OR) of disease, including risk assessments for the MetS factors: obesity (BMI>30 kg m(-2)), hypertension (blood pressure > or =140/90 mmHg or use of anti-hypertensive drugs) and hyperglycaemia (fasting glucose > or =6.1 mmol l(-1) or post-load glucose in capillary plasma > or =8.9 mmol l(-1)).. None of the studied variables were significantly associated with risk across quartiles. Presence of obesity, hypertension and hyperglycaemia significantly increased the risk of colorectal cancer; OR for three vs null factors was 2.57 (95% Confidence Interval [CI] 1.20-5.52; P (trend)=0.0021), as compared to a 30 to 70% increased risk for the factors in single. Similarly, top decile levels of C-peptide, HbA1c and leptin/adiponectin ratio were associated with an increased risk; ORs for top vs deciles 1-9 were 1.56 (95% CI 0.93-2.62; P=0.090), 1.83 (95% CI 1.00-3.36; P=0.051) and 1.50 (95% CI 0.83-2.71; P=0.18), respectively.. Our study support the view that components of the MetS increase risk of colorectal cancer, and further suggests that only very high levels of metabolic factors confer an increased risk.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Colorectal Neoplasms; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Sweden

The physical inactivity and obesity involved in hyperglycemia and hyperinsulinemia is supposed to lead to an increased bioavailability of insulin-like growth factor-I (IGF-I). The carcinogenic effect of IGF-I may be influenced by IGF binding proteins. We investigated the association between plasma levels of C-peptide, a surrogate biomarker of insulin, IGFBP-1, IGF-I or IGFBP-3, and the risk of colorectal cancer in a nested case-control study. During an 11.5-year follow-up, 375 newly diagnosed colorectal cancers were identified in a cohort of 38,373 adults who had returned the baseline questionnaire and provided blood samples. Two matched-controls for each case were selected from the cohort. The odds ratio (OR) of colorectal cancer for plasma levels of each protein was estimated using the conditional logistic regression model adjusted for potential confounding factors. We observed a statistically significant association of plasma C-peptide with colorectal cancer only in men. The ORs were 1.0, 2.3, 2.8 and 3.2 along with quartiles (p trend, 0.0072). The association was stronger in colon cancer (p trend, 0.025) than in rectal cancer (p trend, 0.24). Other peptides were not associated with the risk in either men or women. The results did not change when repeatedly analyzed by tumor invasion levels, tumor sites or follow-up periods. In conclusion, a higher plasma C-peptide may indicate a subsequent risk of colorectal cancer in Japanese men.

Topics: Adult; Aged; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Middle Aged; Prospective Studies

Our aim was to establish whether individuals who developed colon cancer have elevated blood levels of insulin-like growth factor-1 (IGF-1).. This was a case/control study in which 52 patients with colon cancer and a corresponding control group were investigated. Data on age, weight, height, and sex of subjects were recorded and levels of IGF-1 and growth hormone, as well as insulin and C-peptide levels, were measured in the morning before eating, 90 min after breakfast and again 90 min after lunch.. We found significantly higher levels of IGF-1 in blood of colon cancer patients compared to the control group. No differences in the levels of growth hormone, insulin and C-peptide in blood were found between colon cancer patients and the control group. It was found that the increase of IGF-1 level was followed by a 3.15-fold increased risk for developing colon cancer. There were no differences in the levels of IGF-1 in blood in all three measurements in the group of colon cancer patients, whereas differences were found in the control group. We found differences in the levels of insulin and C-peptide in blood in all three measurements in both groups of patients. No differences were found in the levels of growth hormone in blood in all three measurements in both groups of patients.. The results of this study suggest a positive correlation between the increased levels of IGF-1 and colon cancer and are thus consistent with the hypothesis that the level of IGF-1 plays an important role in the development of colon cancer.

Topics: Adult; Aged; Aged, 80 and over; C-Peptide; Case-Control Studies; Cohort Studies; Colonic Neoplasms; Colorectal Neoplasms; Female; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Male; Middle Aged; Risk Factors

Colon carcinogenesis is a multi-steps process in which many growth factors are involved. In some studies the increased risk of colon cancer development was observed in patients with diabetes mellitus type 2 with accompanying hyperinsulinemia. It is also known that insulin-like growth factor I (IGF-I) plays an important role in proliferation, growth, differentiation and inhibiting apoptosis of both epithelial and carcinoma cells. The aim of the study was to evaluate the serum concentration of insulin, C-peptide and IGF-I in patients with colon adenomas and colorectal cancer.. In 17 patients with colon cancer, 32 patients with colon adenomas and in 12 healthy persons the serum concentration of insulin, C-peptide and IGF-I was determined using ELISA kits.. In patients with colon cancer significantly higher serum IGF-I concentration comparing to the control group was observed (85.66 ng/ml vs. 60.96 ng/ml; p < 0.05). Higher IGF-I concentration was also observed in patients with distal tumors comparing to the proximal localisation (95.40 ng/ml vs. 64,65 ng/ml, p < 0.05) and in more differentiated tumors (84.36 ng/ml vs. 75.24 ng/ml). Similarly, higher C-peptide concentrations were observed in distal tumors (635.64 pmol/ I vs. 578.69 pmol/l) and in well-differentiated carcinoma (671.32 pmol/ I vs. 575.66 pmol/l). In patients with colon adenomatous polyps we also observed higher serum IGF-I concentrations I comparing to the control group (82.1 ng/ml vs. 60.96 ng/ml), in high dysplasia adenomas (84.12 ng/ml vs. 79.67 ng/ml) and in smaller adenomas to 1 cm diameter (97.98 ng/ml vs. 73.28 ng/ml), but the differences were not significant. We also observed higher concentration of C-peptide in patients with low grade dysplasia adenomas (665.24 pmol/l vs. 498.13 pmol/l) and with small polyps (611.51 pmol/l vs. 514.89 pmol/l). There were no differences in serum concentration of IGF-I and C-peptide between patients with tubular and villous adenomas. There was no statistical difference observed in insulin serum concentration in all groups of patients.. IGF-I is probably involved particularly in the early stage of colon carcinogenesis.

Topics: Adenoma; Adenomatous Polyps; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; C-Peptide; Colonic Polyps; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Female; Humans; Hyperinsulinism; Insulin; Insulin-Like Growth Factor I; Male; Middle Aged

Determinants of insulin secretion and insulin-like growth factors (IGF) have been directly associated with risk for colorectal cancer. However, few studies have evaluated whether these factors are also associated with risk of colorectal adenoma, the main precursor lesion to colorectal cancer.. We identified 380 distal colorectal adenoma cases diagnosed between 1989 and 1998 and 380 controls among nondiabetic women from the cohort of 32,826 women, nested in the Nurses' Health Study, who provided blood samples in 1989 to 1990. Cases and controls were individually matched on year of birth, time period of and indication(s) for endoscopy, and date of blood draw.. High concentrations of C-peptide, an indicator of insulin secretion, were statistically significantly associated with risk of distal colorectal adenoma [multivariable relative risk (MVRR) top versus bottom quartile, 1.63; 95% confidence interval (95% CI), 1.01-2.66; P = 0.01], even after including body mass index and physical activity in the statistical model. Fasting IGF binding protein-1 (IGFBP-1) concentrations did not show any clear association with risk for adenoma (MVRR top versus bottom quartile, 1.08; 95% CI, 0.56-2.07). These associations did not differ significantly by size/stage of adenoma. Glycosylated hemoglobin (HbA1c) was associated with a nonstatistically significant increased risk of colorectal adenoma (MVRR top versus bottom quartile, 1.47; 95% CI, 0.89-2.44).. High HbA1c and low IGFBP-1 were not clearly associated with increased risk of distal colorectal adenoma. However, our current results and previous associations between C-peptide and colorectal cancer suggest that hyperinsulinemia may play a role throughout the development of colorectal neoplasia.

Topics: Adenoma; Adult; C-Peptide; Colorectal Neoplasms; Female; Glycated Hemoglobin; Humans; Hyperinsulinism; Insulin-Like Growth Factor Binding Protein 1; Middle Aged; Prospective Studies; Risk

Some studies have found that people with type 2 diabetes mellitus are at increased risk of neoplasms, especially colorectal cancer (CRC). In other studies it is also suggested that there is a higher incidence of diabetes mellitus in patients with CRC. The aims of this study were to assess whether the incidence of type 2 diabetes mellitus and impaired glucose tolerance (IGT) are higher in subjects with CRC and to determine the difference between diabetic subjects and healthy controls regarding glucose metabolism (glycaemia, insulinaemia, serum levels of C-peptide) as well as insulin resistance and sensitivity.. The study included a total of 80 subjects: 40 enrolled patients (20 M, 20 F) with newly diagnosed sporadic colorectal cancer and 40 subjects with endoscopically excluded CRC or adenomas serving as controls. Subjects were matched for gender, age and body mass index (BMI) (age +/- 5 years BMI +/- 1 kg/m2). A 75-g oral glucose tolerance test was performed after an overnight fast. Samples for glycaemia, serum levels of C-peptide and insulin were taken at 0, 30, 60, 90, 120 and 150 min of the study. HOMA-IR, EIR, EIR/HOMA-IR indexes were calculated.. There was a significantly higher incidence of impaired glucose metabolism (IGM-diabetes mellitus or IGT) in CRC subjects. No differences were found in levels of glucose, insulin or C-peptide. Insulinaemia and C-peptide curves showed a shift typical of diabetes, in the form of a delayed insulin release peak. The HOMA-IR, EIR as well as the EIR/HOMA-IR indexes showed no differences between groups.. A significantly higher incidence of IGM appears to occur in CRC patients than in the healthy population. This phenomenon is not dependent on age and body-weight, which may suggest that it is cancer that predisposes to diabetes rather than the other way round. The neoplastic process in the colon is not associated with hyperinsulinaemia or insulin resistance, but in CRC patients, pancreatic B-cell dysfunction typical of the early stages of diabetes is seen.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; C-Peptide; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Prevalence; Prognosis; Retrospective Studies; Risk Factors

Hyperinsulinemia, hyperglycemia, and elevated insulin-like growth factor (IGF)-1 levels have been implicated in the etiology of colorectal cancer. However, the joint effects of insulin and IGF-I have not been considered, and whether hyperinsulinemia or hyperglycemia is more etiologically relevant is unclear. IGF binding protein-1 (IGFBP-1) has been hypothesized to mediate the effects of insulin, but epidemiologic data on IGFBP-1 are sparse. We conducted a nested case-control study among the 32,826 women of the Nurses' Health Study who provided a blood sample in 1989 to 1990. After excluding diabetics, we confirmed 182 incident colorectal cancer cases over 10 years of follow-up and 350 controls. Cases were matched to two controls on year of birth, date of blood draw, and fasting status. C-peptide levels were weakly associated with risk of colon cancer [top quartile (Q4) versus bottom quartile (Q1): multivariable relative risk (MVRR), 1.76; 95% confidence interval (95% CI), 0.85-3.63]. Fasting IGFBP-1 was inversely associated with risk of colon cancer (MVRR, 0.28; 95% CI, 0.11-0.75). We observed no clear association between glycosylated hemoglobin and risk for colorectal cancer. The IGF-I to IGFBP-3 molar ratio was associated with colon cancer risk (MVRR, 2.82; 95% CI, 1.35-5.88), and women with low levels of both IGF-I/IGFBP-3 and C-peptide (or high IGFBP-1) were at low risk, and elevation of either was sufficient to increase risk. Although altering IGF-I levels may not be practical, the growing burden of obesity and consequently hyperinsulinemia, which seems increasingly important for colon cancer, may be a target for effective prevention.

Topics: Adult; Biomarkers, Tumor; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Hyperglycemia; Hyperinsulinism; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Middle Aged; Prospective Studies

Predictors of quality of life (QOL) in patients with metastatic colorectal cancer are lacking. The insulin-like growth factor (IGF) family of proteins is associated with QOL in noncancer populations. We sought to study whether these proteins are associated with QOL in patients with colorectal cancer.. We used a cohort of 526 patients with metastatic colorectal cancer treated with combination chemotherapy. Plasma samples of IGF-I, IGF-II, IGF binding protein-3, and C-peptide were collected before initiation of chemotherapy. QOL was measured by the uniscale instrument and the Symptom Distress Scale at baseline and throughout treatment.. Baseline plasma levels of IGF-I and IGF-II before initiation of chemotherapy were significantly associated with several important baseline QOL measures in patients with metastatic colorectal cancer. Patients with lower levels of IGF-I reported increased distress with regard to appearance, appetite, cough, and nausea intensity after adjustment for potential confounders. Similarly, decreased levels of IGF-II were predictive of worse quality related to appearance, appetite, fatigue, nausea frequency and intensity, pain frequency, and composite Symptom Distress Scale score. IGF binding protein-3 and C-peptide were not predictive of baseline QOL. Baseline biomarkers were not associated with subsequent changes in QOL during treatment. Higher body mass index was significantly associated with superior baseline QOL in several areas; nonetheless, the association of IGF-I and IGF-II with baseline QOL measures remained significant even after controlling for baseline body mass index.. Baseline plasma IGF-I and IGF-II are significantly associated with symptom distress. Whether this association is simply reflective of patient nutritional status and/or disease burden or represents an independent biological effect of IGFs on QOL remains uncertain. Nonetheless, these data suggest that molecular biomarkers may be useful predictors of QOL in cancer patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appetite; Biomarkers, Tumor; C-Peptide; Cohort Studies; Colorectal Neoplasms; Fatigue; Female; Humans; Male; Middle Aged; Nausea; Neoplasm Metastasis; Patient Satisfaction; Quality of Life; Somatomedins; Stress, Psychological

Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44-5.12) for top vs. bottom quartile (p(trend) = 0.008). The corresponding OR for C-peptide was 1.81 (95% CI = 0.67-4.86; p(trend) = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C-peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.

Topics: Adult; C-Peptide; Case-Control Studies; Colonic Neoplasms; Colorectal Neoplasms; Cryopreservation; Humans; Insulin; Leptin; Logistic Models; Male; Middle Aged; Obesity; Odds Ratio; Registries; Time Factors

Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia appears to be associated with an increased risk of colorectal cancer. We used the concentration of plasma C-peptide (an indicator of insulin production) to determine whether insulin and insulin resistance are associated with the risk of developing colorectal cancer.. We conducted a nested case-control study in the Physicians' Health Study. Plasma samples were collected from 14 916 cancer-free men from August 1982 through December 1984. Plasma C-peptide concentration, measured with an enzyme-linked immunosorbent assay, was available for 176 case patients who developed incident colorectal cancer through December 31, 1995, and 294 age- and smoking status-matched control subjects. Information on four other insulin resistance-related factors at baseline was obtained. We used conditional logistic regression models to investigate associations. All statistical tests were two-sided.. Plasma C-peptide concentration was positively associated with age, body mass index (BMI), and number of insulin resistance-related factors, and it was inversely associated with fasting time before the blood draw, alcohol consumption, and vigorous exercise. An increased concentration of plasma C-peptide was statistically significantly associated with an increased risk of colorectal cancer (relative risk [RR] for the highest versus lowest quintile of plasma C-peptide = 2.7, 95% confidence interval [CI] = 1.2 to 6.2; P(trend) =.047), after adjusting for age, smoking status, fasting, BMI, alcohol consumption, vigorous exercise, and aspirin assignment in the Physicians' Health Study. The association became even stronger when the analysis was further adjusted for factors related to insulin resistance other than insulin levels (RR for the highest versus lowest quintile = 3.4, 95% CI = 1.4 to 8.3; P(trend) =.02) or when data from case patients who were diagnosed during the first 5 years of follow-up were excluded (RR for the highest versus the lowest quintile = 3.4, 95% CI = 1.3 to 8.8; P(trend) =.03). Adjusting for plasma levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) did not materially change the results. There was no apparent modification of risk by BMI, insulin resistance-related factors, or vigorous exercise.. Elevated insulin production, as reflected by elevated concentrations of plasma C-peptide, may predict the risk of developing colorectal cancer, independently of BMI, factors related to insulin resistance, or levels of IGF-I and IGFBP-3.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Body Mass Index; Boston; C-Peptide; Case-Control Studies; Cluster Analysis; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Logistic Models; Male; Middle Aged; Physicians; Predictive Value of Tests; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; United States

Leading a Western lifestyle, being overweight, and being sedentary are associated with an increased risk of colorectal cancer. Recent theories propose that the effects of these risk factors may be mediated by increases in circulating insulin levels and in the bioactivity of insulin-like growth factor (IGF)-I. To test this hypothesis, we conducted a case-control study nested within a cohort of 14 275 women in New York.. We used blood samples that had been obtained from these women from March 1985 through June 1991 and stored in a biorepository. C-peptide (a marker for insulin secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were assayed in the serum of 102 women who subsequently developed colorectal cancer and 200 matched control subjects. Logistic regression was used to relate cancer risk to these peptide levels, by adjustment for other risk factors. All statistical tests used are two-sided.. Colorectal cancer risk increased with increasing levels of C-peptide (P:(trend) =.001), up to an odds ratio (OR) of 2. 92 (95% confidence interval [CI] = 1.26-6.75) for the highest versus the lowest quintiles, after adjustment for smoking. For colon cancer alone (75 case subjects and 146 control subjects), ORs increased up to 3.96 (95% CI = 1.49-10.50; P:(trend) <.001) for the highest versus the lowest quintiles. A statistically significant decrease in colorectal cancer risk was observed for increasing levels of IGFBP-1 (P:(trend) =.02; OR in the upper quintile = 0.48 [95% CI = 0.23-1. 00]), as well as for the highest quintile of IGFBP-2 levels (P:(trend) =.06; OR = 0.38 [95% CI = 0.15-0.94]). Colorectal cancer risk showed a modest but statistically nonsignificant positive association with levels of IGF-I and was statistically significantly increased for the highest quintile of IGFBP-3 (OR = 2.46 [95% CI = 1. 09-5.57]).. Chronically high levels of circulating insulin and IGFs associated with a Western lifestyle may increase colorectal cancer risk, possibly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I.

Topics: Adult; Body Mass Index; C-Peptide; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Logistic Models; Middle Aged; New York; Odds Ratio; Prospective Studies; Risk; Risk Factors