c-peptide and Colonic-Neoplasms

C-peptide, a hormone secreted by the pancreas, is a marker for insulin production and hyperinsulinemia. Epidemiological studies have suggested an association between circulating C-peptide level and colorectal neoplasia risk; however, the results were not always consistent. Herein, we conducted a systematic review and meta-analysis study to evaluate the association between circulating C-peptide level and the colorectal neoplasia risk.. The PubMed database was searched for the eligibility studies updated to May 2013, which prospectively evaluated the association between circulating C-peptide level and colorectal neoplasia risk. The summary estimates and 95 % confidential intervals (95 % CIs) for those with the highest quantile C-peptide level in contrast to the lowest quantile were estimated with the random-effects model. Heterogeneity between the studies was assessed with the Q test and the I (2) statistic. Potential publication bias was evaluated with the Egger's test.. We identified 9 nested case-control studies that have recruited a total of 3,109 cases and 4,285 controls met the criteria. From the meta-analysis, we found that subjects with high circulating C-peptide were associated with a 37 % increased colorectal neoplasia risk [pooled odds ratios (OR) 1.37, 95 % CI 1.09-1.72] under the random-effects model. In the stratification studies, we found the association was more prominent in the men (pooled OR 2.34, 95 % CI 1.36-4.04) compared to women (pooled OR 1.41, 95 % CI 0.89-2.25). Significant association between circulating C-peptide level and colon cancer risk was found (pooled OR 1.72, 95 % CI 1.26-2.36), but not for rectal cancer (pooled OR 1.14, 95 % CI 0.75-1.73). No significant publication bias was found for any meta-analysis study.. In conclusion, the results of the meta-analysis studies suggested that higher circulating C-peptide could be a predictive factor for higher colorectal neoplasia susceptibility.

Topics: Biomarkers, Tumor; C-Peptide; Colonic Neoplasms; Female; Humans; Male; Prospective Studies

Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study.. Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression.. The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05).. These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.

Topics: Adiponectin; Aged; Black or African American; C-Peptide; Colonic Neoplasms; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Genotyping Techniques; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Logistic Models; Male; Middle Aged; Polymorphism, Genetic; Risk Factors; White People

Aspirin use decreases colon cancer risk, but this association may vary among population subgroups. The aspirin-colon cancer association was evaluated according to body mass index and physical activity in 1,701 incident colon cancer cases diagnosed during follow-up of 139,310 participants for up to 26 years in 2 US prospective cohort studies that began in 1980 and 1992, respectively. Whether plasma C-peptide levels modified the association was examined by using a nested case-control design (n = 384 cases, 749 controls). Multiplicative and additive interactions were tested. Body mass index did not modify the association; pooled multivariable relative risks for regular aspirin use versus nonuse ranged from 0.74 to 0.75 in the normal weight and obese groups (test for multiplicative interaction, P = 0.75; test for additive interaction, P = 0.66). Pooled multivariable relative risks for regular aspirin use were 0.86 (95% confidence interval (CI): 0.66, 1.11) in the low and 0.67 (95% CI: 0.58, 0.77) in the high physical activity groups with no interaction evident on either the multiplicative or additive scale (P > 0.10). Plasma C-peptide levels also did not modify the aspirin-colon cancer association, with multivariable relative risks of 0.74 (95% CI: 0.50, 1.10) for the low and 0.65 (95% CI: 0.46, 0.92) for the high group. Reductions in colon cancer risk associated with aspirin use were not significantly modified by body mass index, physical activity, or plasma C-peptide level in this study.

Topics: Adult; Aged; Aspirin; Body Mass Index; C-Peptide; Case-Control Studies; Chi-Square Distribution; Colonic Neoplasms; Female; Health Personnel; Humans; Incidence; Male; Middle Aged; Motor Activity; Prospective Studies; Risk; Surveys and Questionnaires; United States

Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB) on formation of aberrant crypt foci (ACF) in colons of male Fisher F344 rats (inbred strain). However, effects of BB on colon tumors and in both genders are unknown.. We examined efficacy of BB in inhibition of azoxymethane (AOM)-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain). Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults.. Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (P < 0.05) ACF numbers within the distal colon of female but not male rats. There was a significant (P < 0.05) diet by gender interaction with respect to total colon ACF number. Colon and duodenum tumor incidences were less in females than males at 17 weeks after AOM. BB tended (0.1 > P > 0.05) to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (P > 0.1) by BB. There was a tendency (0.1 > P > 0.05) for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas) in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (P < 0.05). BB favored (P < 0.05) fewer adenocarcinomas and more adenomatous polyps (as a proportion of total tumor number) in female rat small intestine.. Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma) by BB.

Topics: Adenocarcinoma; Adenomatous Polyps; Animals; Azoxymethane; Blueberry Plants; C-Peptide; Colonic Neoplasms; Disease Models, Animal; Disease Progression; Duodenal Neoplasms; Female; Incidence; Male; Nutrition Therapy; Rats; Rats, Sprague-Dawley

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

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

Proteinase-activated receptors (PARs) are activated by proteolytic removal of a short amino terminal peptide, thus exposing a new amino terminus that functions as a tethered ligand that activates the receptor. With the aim to identify and study potential activators of PAR-2 we have developed a new method to measure proteolytic cleavage of PARs. PAR-2 was tagged with the insulin C-peptide that upon receptor cleavage is released and quantified using an ELISA. The modified receptor, shown to be functional in mouse 3T3 cells, was expressed in an insect cell line and the ability of different proteinases to cleave PAR-2 was studied. Two different mast cell tryptases cleaved PAR-2 in a concentration dependent manner, but were much less potent than pancreatic trypsin and trypsin-2 isolated from a carcinoma cell line. Pancreatic trypsin and trypsin-2 were almost equally effective at cleaving PAR-2 suggesting that extrapancreatic trypsins are potential in vivo activators of PAR-2.

Topics: 3T3 Cells; Amino Acid Sequence; Animals; C-Peptide; Calcium; Catalysis; Cattle; Chymases; Colonic Neoplasms; Enzyme-Linked Immunosorbent Assay; Humans; Mast Cells; Mice; Molecular Sequence Data; Pancreas; Receptor, PAR-2; Receptors, Thrombin; Recombinant Fusion Proteins; Serine Endopeptidases; Thrombin; Trypsin; Tryptases; Tumor Cells, Cultured