| 1. |
- Aleksandrova, Krasimira, et al.
(författare)
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Metabolic syndrome and risks of colon and rectal cancer : the European prospective investigation into cancer and nutrition study.
- 2011
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Ingår i: Cancer prevention research (Philadelphia, Pa.). - 1940-6215. ; 4:11, s. 1873-83
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic syndrome (MetS) is purportedly related to risk of developing colorectal cancer; however, the association of MetS, as defined according to recent international criteria, and colorectal cancer has not been yet evaluated. In particular, it remains unclear to what extent the MetS components individually account for such an association. We addressed these issues in a nested case-control study that included 1,093 incident cases matched (1:1) to controls by using incidence density sampling. Conditional logistic regression was used to estimate relative risks (RR) and 95% CIs. MetS was defined according to the criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII), the International Diabetes Federation (IDF), and the 2009 harmonized definition. Among individual components, abdominal obesity (RR = 1.51; 95% CI: 1.16-1.96) was associated with colon cancer, whereas abnormal glucose metabolism was associated with both colon (RR = 2.05; 95% CI: 1.57-2.68) and rectal cancer (RR = 2.07; 95% CI: 1.45-2.96). MetS, as defined by each of the definitions, was similarly associated with colon cancer (e.g., RR = 1.91; 95% CI: 1.47-2.42 for MetS by NCEP/ATPIII), whereas MetS by NCEP/ATPIII, but not IDF or harmonized definition, was associated with rectal cancer (RR = 1.45; 95% CI: 1.02-2.06). Overall, these associations were stronger in women than in men. However, the association between MetS and colorectal cancer was accounted for by abdominal obesity and abnormal glucose metabolism such that MetS did not provide risk information beyond these components (likelihood ratio test P = 0.10 for MetS by NCEP/ATPIII). These data suggest that simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions. Cancer Prev Res; 4(11); 1873-83. ©2011 AACR.
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| 2. |
- Campa, Daniele, et al.
(författare)
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Genetic variability of the mTOR pathway and prostate cancer risk in the European prospective investigation on cancer (EPIC)
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2, s. e16914-
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Tidskriftsartikel (refereegranskat)abstract
- The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p<0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (OR(allele) = 0.85, 95% CI 0.78-0.94, p = 1.3×10(-3) for rs546950 and OR(allele) = 0.84, 95% CI 0.76-0.93, p = 5.6×10(-4) for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.
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| 3. |
- Dossus, Laure, et al.
(författare)
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Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk : the EPIC study
- 2011
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 129:8, s. 2032-2037
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, Ptrend = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.
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| 4. |
- Fedirko, Veronika, et al.
(författare)
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Prediagnostic circulating parathyroid hormone concentration and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition cohort
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:5, s. 767-778
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC). METHODS: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating prediagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95% CI) for the association between circulating PTH and CRC risk. RESULTS: In multivariate analyses [including adjustment for 25(OH)D concentration] with a priori defined cutoff points, high levels of serum PTH (≥65 ng/L) compared with medium PTH levels of 30-65 ng/L were associated with increased CRC risk (RR = 1.41, 95% CI: 1.03-1.93). In analyses by sex, the CRC risk was 1.77 (95% CI: 1.14-2.75) and 1.15 (95% CI: 0.73-1.84) in men and women, respectively (P(heterogeneity) = 0.01). In subgroup analyses by anatomical subsite, the risk for colon cancer was RR = 1.56, 95% CI: 1.03-2.34, and for rectal cancer RR = 1.20, 95% CI: 0.72-2.01 (P(heterogeneity) = 0.21). Effect modification by various risk factors was examined. CONCLUSIONS: The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men. IMPACT: To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated.
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| 5. |
- Leufkens, Anke M, et al.
(författare)
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Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location
- 2011
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Ingår i: International Journal of Cancer. - New York : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 130:3, s. 622-630
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Tidskriftsartikel (refereegranskat)abstract
- Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57–0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58–0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe.
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| 6. |
- Sluik, Diewertje, et al.
(författare)
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Associations Between General and Abdominal Adiposity and Mortality in Individuals With Diabetes Mellitus
- 2011
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Ingår i: American Journal of Epidemiology. - Cary : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 174:1, s. 22-34
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with diabetes mellitus are advised to achieve a healthy weight to prevent complications. However, fat mass distribution has hardly been investigated as a risk factor for diabetes complications. The authors studied associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus. Within the European Prospective Investigation into Cancer and Nutrition, a subcohort was defined as 5,435 individuals with a confirmed self-report of diabetes mellitus at baseline in 1992-2000. Participants were aged 57.3 (standard deviation, 6.3) years, 54% were men, the median diabetes duration was 4.6 (interquartile range, 2.0-9.8) years, and 22% of the participants used insulin. Body mass index, as indicator of general obesity, was not associated with higher mortality, whereas all measurements of abdominal obesity showed a positive association. Associations generally were slightly weaker in women. The strongest association was observed for waist/height ratio: In the fifth quintile, the hazard rate ratio was 1.88 (95% confidence interval: 1.33, 2.65) for men and 2.46 (95% confidence interval: 1.46, 4.14) for women. Measurements of abdominal, but not general, adiposity were associated with higher mortality in diabetic individuals. The waist/height ratio showed the strongest association. Respective indicators might be investigated in risk prediction models.
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| 7. |
- Trichopoulos, Dimitrios, et al.
(författare)
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Hepatocellular carcinoma risk factors and disease burden in a European cohort : a nested case-control study
- 2011
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Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford University Press. - 0027-8874 .- 1460-2105. ; 103:22, s. 1686-1695
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Tidskriftsartikel (refereegranskat)abstract
- Background: To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors.Methods: Using data collected from 1992 to 2006, which included 4 409 809 person-years in the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 125 case patients with hepatocellular carcinoma, of whom 115 were matched to 229 control subjects. We calculated odds ratios (ORs) for the association of documented risk factors for hepatocellular carcinoma with incidence of this disease and estimated their importance in this European cohort.Results: Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (OR = 9.10, 95% confidence interval [CI] = 2.10 to 39.50 and OR = 13.36, 95% CI = 4.11 to 43.45, respectively), obesity (OR = 2.13, 95% CI = 1.06 to 4.29), former or current smoking (OR = 1.98, 95% CI = 0.90 to 4.39 and OR = 4.55, 95% CI = 1.90 to 10.91, respectively), and heavy alcohol intake (OR = 1.77, 95% CI = 0.73 to 4.27) were associated with hepatocellular carcinoma. Smoking contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively. Obesity and heavy alcohol intake contributed 16.1% and 10.2%, respectively. Almost two-thirds (65.7%, 95% CI = 50.6% to 79.3%) of hepatocellular carcinomas can be accounted for by exposure to at least one of these documented risk factors.Conclusions: Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections. Heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden. These contributions may be underestimates because EPIC volunteers are likely to be more health conscious than the general population.
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| 8. |
- van Duijnhoven, Fränzel J B, et al.
(författare)
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Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition
- 2011
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Ingår i: Gut. - London : BMJ Publishing. - 0017-5749 .- 1468-3288. ; 60:8, s. 1094-1102
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). DESIGN: Nested case-control study. SETTING: The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520,000 participants from 10 western European countries. PARTICIPANTS: 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. MAIN OUTCOME MEASURES: Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. RESULTS: After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. CONCLUSIONS: These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation.
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