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- Aleksandrova, Krasimira, et al.
(författare)
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Total and high-molecular-weight adiponectin and risk of colorectal cancer : the European prospective investigation into cancer and nutrition study
- 2012
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 33:6, s. 1211-1218
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin - an adipose-tissue-derived protein may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular-weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite they were hypothesised to have differential biological activities, i.e. regulating insulin sensitivity (HMW-adiponectin) versus inflammatory response (non-HMW-adiponectin). In a prospective nested case-control study we investigated whether pre-diagnostic serum concentrations of total, HMW and non-HMW-adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon, 451 rectal) were matched to 1206 controls using incidence density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW-adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P (trend)=0.03 for total adiponectin and 0.45, 95%CI=0.34-0.61, P (trend)<0.0001 for non-HMW-adiponectin]. HMW-adiponectin concentrations were not associated with CRC risk (RR=0.91, 95%CI=0.68-1.22, P (trend)=0.55). Non-HMW-adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR=0.39, 95%CI=0.26-0.60, P (trend)<0.0001); whereas the association with total adiponectin was no longer significant (RR=0.81, 95%CI=0.60-1.09, P (trend)=0.23). When stratified by cancer site, non-HMW-adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW-adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.
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| 2. |
- Grote, Verena A., et al.
(författare)
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The association of circulating adiponectin levels with pancreatic cancer risk: A study within the prospective EPIC cohort
- 2012
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 130, s. 2428-2437
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Tidskriftsartikel (refereegranskat)abstract
- Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development. © 2011 UICC.
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| 3. |
- Grote, Verena A., et al.
(författare)
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The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: A case-control study within the prospective EPIC cohort
- 2012
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 21:4, s. 619-628
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Tidskriftsartikel (refereegranskat)abstract
- Background: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. Methods: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). Results: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P interaction = 0.002). Conclusions and Impact: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations. ©2012 AACR.
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| 4. |
- Jakszyn, Paula G, et al.
(författare)
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Nitrosamines and Heme Iron and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition.
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 21:3, s. 547-551
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The evidence about nitrosamines and heme iron intake and cancer risk is limited, despite the biologic plausibility of the hypothesis that these factors might increase cancer risk. We investigated the association between dietary nitrosamines and heme iron and the risk of prostate cancer among participants of European Prospective Investigation into Cancer and Nutrition (EPIC).METHODS: Data on food consumption and complete follow-up for cancer occurrence was available for 139,005 men, recruited in 8 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, and study center, and adjusted for total energy intake, smoking status, marital status, dairy products, educational level, and body mass index.RESULTS: After a mean follow-up of 10 years, 4,606 participants were diagnosed with first incident prostate cancer. There was no overall association between prostate cancer risk and nitrosamines exposure (preformed and endogenous) or heme iron intake (HR for a doubling of intake: 1.00; 95% CI: 0.98-1.03 for N-Nitrosodimethlyamine, 0.95; 95% CI: 0.88-1.03 for endogenous Nitrosocompounds, and 1.00; 95 CI: 0.97-1.03 for heme iron).Conclusions and Impact: Our findings do not support an effect of nitrosamines (endogenous and exogenous) and heme iron intake on prostate cancer risk.
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| 5. |
- Leufkens, Anke M, et al.
(författare)
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Biomarkers of oxidative stress and risk of developing colorectal cancer : a cohort-nested case-control study in the European Prospective Investigation into Cancer and Nutrition
- 2012
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 175:7, s. 653-663
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR(adj)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR(adj) = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.
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