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  • 1
    Keywords: ENERGIES ; CANCER ; MODEL ; FOLLOW-UP ; POPULATION ; RISK ; ASSOCIATION ; hormone ; ENERGY ; AGE ; WOMEN ; colorectal cancer ; MEN ; PROSPECTIVE COHORT ; smoking ; COLORECTAL-CANCER ; cancer risk ; FISH ; FIBER ; COLON-CANCER ; DOSE-RESPONSE ; Jun ; DIET ; DIETARY ; UNITED-STATES ; ALCOHOL-CONSUMPTION ; nutrition ; ASSOCIATIONS ; RE ; ENERGY-INTAKE ; EPIC CALIBRATION ; PHYSICAL-ACTIVITY ; INTERVAL ; TESTS ; alcohol consumption ; MEAT INTAKE ; DIETARY CARCINOGENS ; GENETIC SUSCEPTIBILITY ; N-NITROSATION ; RED MEAT
    Abstract: Background. Current evidence suggests that high red meat intake is associated with increased colorectal cancer risk. High fish intake may be associated with a decreased risk, but the existing evidence is less convincing. Methods: We prospectively followed 478040 men and women from 10 European countries who were free of cancer at enrollment between 1992 and 1998. Information on diet and lifestyle was collected at baseline. After a mean follow-up of 4.8 years, 1329 incident colorectal cancers were documented. We examined the relationship between intakes of red and processed meat, poultry, and fish and colorectal cancer risk using a proportional hazards model adjusted for age, sex, energy (nonfat and fat sources), height, weight, work-related physical activity, smoking status, dietary fiber and folate, and alcohol consumption, stratified by center. A calibration substudy based on 36994 subjects was used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. All statistical tests were two-sided. Results: Colorectal cancer risk was positively associated with intake of red and processed meat (highest [〉 160 g/day] versus lowest [〈 20 g/day] intake, HR = 1.35, 95% CI = 0.96 to 1.88; P-trend = .03) and inversely associated with intake of fish (〉 80 g/day versus 〈 10 g/day, HR = 0.69, 95% CI = 0.54 to 0.88; P-trend 〈 .001), but was not related to poultry intake. Correcting for measurement error strengthened the associations between colorectal cancer and red and processed meat intake (per 100-g increase HR = 1.25, 95% CI = 1.09 to 1.41, P-trend = .001 and HR = 1.55, 95% CI = 1.19 to 2.02, P-trend = .001 before and after calibration, respectively) and for fish (per 100 g increase HR = 0.70, 95% CI = 0.57 to 0.87, P-trend 〈 .001 and HR = 0.46, 95% CI = 0.27 to 0.77, P-trend = .003; before and after correction, respectively). In this study population, the absolute risk of development of colorectal cancer within 10 years for a study subject aged 50 years was 1.71% for the highest category of red and processed meat intake and 1.28% for the lowest category of intake and was 1.86% for subjects in the lowest category of fish intake and 1.28% for subjects in the highest category of fish intake. Conclusions: Our data confirm that colorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fish intake
    Type of Publication: Journal article published
    PubMed ID: 15956652
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  • 2
    Keywords: EXPOSURE ; INDEX ; POPULATIONS ; QUESTIONNAIRE ; SMOKERS ; FOOD ; fat distribution ; HEMOGLOBIN ADDUCTS
    Abstract: BACKGROUND: In 1994, acrylamide (AA) was classified as a probable human carcinogen by the International Agency for Research on Cancer. In 2002, AA was discovered at relatively high concentrations in some starchy, plant-based foods cooked at high temperatures. PATIENTS AND METHODS: A prospective analysis was conducted to evaluate the association between the dietary intake of AA and ductal adenocarcinoma of the exocrine pancreatic cancer (PC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort using Cox regression modeling. EPIC includes 〉500,000 men and women aged 35-75 at enrollment from 10 European countries. AA intake was estimated for each participant by combining questionnaire-based food consumption data with a harmonized AA database derived from the EU monitoring database of AA levels in foods, and evaluated in quintiles and continuously. RESULTS: After a mean follow-up of 11 years, 865 first incident adenocarcinomas of the exocrine pancreas were observed and included in the present analysis. At baseline, the mean dietary AA intake in EPIC was 26.22 microg/day. No overall association was found between continuous or quintiles of dietary AA intake and PC risk in EPIC (HR:0.95, 95%CI:0.89-1.01 per 10 microg/day). There was no effect measure modification by smoking status, sex, diabetes, alcohol intake or geographic region. However, there was an inverse association (HR: 0.73, 95% CI: 0.61-0.88 per 10 microg/day) between AA intake and PC risk in obese persons as defined using the body mass index (BMI, 〉/= 30 kg/m(2)), but not when body fatness was defined using waist and hip circumference or their ratio. CONCLUSIONS: Dietary intake of AA was not associated with an increased risk of PC in the EPIC cohort.
    Type of Publication: Journal article published
    PubMed ID: 23857962
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  • 3
    Keywords: LUNG-CANCER ; EPIDEMIOLOGY ; RISK-FACTORS ; PLASMA ; MARKERS ; MASS-SPECTROMETRY ; nutrition ; KIDNEY CANCER ; MICROBIOLOGICAL ASSAY ; FOLATE
    Abstract: Background The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival. Methods The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385 747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided. Results EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4th and 1st quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P-trend 〈 .001. We found similar results after adjusting for potential confounders (adjusted P-trend 〈 .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4th and 1st quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P-trend 〈 .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P-trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P-trend = .02). No association was evident for the other measured biomarkers. Conclusion Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts.
    Type of Publication: Journal article published
    PubMed ID: 25376861
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  • 4
    Abstract: BACKGROUND: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death. METHODS: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models. RESULTS: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31-32 %) and 14 % (95 % CI, 12-16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8-12 %) and high blood pressure (9 %; 95 % CI, 7-11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55-59 %), being 35 % (95 % CI, 32-37 %) among never smokers and 74 % (95 % CI, 73-75 %) among current smokers. CONCLUSIONS: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed.
    Type of Publication: Journal article published
    PubMed ID: 27296932
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  • 5
    Keywords: CANCER ; BLOOD ; Germany ; MODEL ; MODELS ; SYSTEM ; DISEASE ; RISK ; RISKS ; PROTEIN ; SAMPLE ; SAMPLES ; METABOLISM ; SERA ; INDEX ; BINDING ; ASSOCIATION ; BREAST-CANCER ; NO ; hormone ; NEOPLASIA ; AGE ; ovarian cancer ; OVARIAN-CANCER ; WOMEN ; COLORECTAL-CANCER ; cancer risk ; case-control studies ; BODY ; EPIC ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; RELATIVE RISK ; REGRESSION-MODELS ; BINDING PROTEIN ; MASS INDEX ; MASSES ; SERUM ; BODIES ; IGF-I ; ONCOLOGY ; BINDING-PROTEIN ; case control study ; case-control study ; REGRESSION ; RE ; DETERMINANTS ; HEIGHT ; development ; GROWTH-FACTOR-I ; LEVEL ; case control studies ; analysis ; BODY-MASS INDEX ; IGFBP3 ; PREMENOPAUSAL ; prospective ; odds ratio ; CANCER-RISK ; CIRCULATING LEVELS ; OVARIAN ; IGFBP-3 ; SET ; LOGISTIC-REGRESSION ; BODY-MASS ; BODY-MASS-INDEX ; INSULIN-LIKE-GROWTH-FACTOR-1
    Abstract: We set out to study the relationship between circulating levels of IGF-I and its major binding protein (IGFBP-3) in relation to ovarian cancer risk. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of IGF-I and IGFBP-3 were measured in prediagnostic serum samples of 214 women who subsequently developed ovarian cancer, and 388 matched control subjects. Conditional logistic regression models were used to estimate relative risks of ovarian cancer by tertiles of IGF-I and IGFBP-3 levels. For all women, there was no association between the circulating IGF-I or IGFBP-3 levels and the risk of ovarian cancer. However, among women diagnosed with ovarian cancer aged 55 or younger, the relative risk was higher in the middle or top tertiles of serum IGF-I, when compared with women in the lowest tertile (odds ratios (OR) = 1.8 (95%Cl 0.7-4.3) and OR = 2.4 (95%Cl 0.9-6.4); P-trend = 0.08) respectively. These results were adjusted for body mass index, previous hormone use, fertility problems, and parity. Restricting the analysis to women who were premenopausal at blood donation, relative risks for ovarian cancer diagnosed before age 55 were higher (OR = 5.1 (95%Cl 1.5-18.2) and OR = 5.6 (95%Cl 1.5-20.8) respectively, for second and third tertiles; P-trend = 0.02). Adjustment for serum IGFBP-3 levels only slightly attenuated relative risk estimates. Relations between IGFBP-3 and ovarian cancer before age 55 were in the same direction as for IGF-I, but less strong and statistically not significant. In women aged over 55, there was no association between serum IGF-I or IGFBP-3 and ovarian cancer risk. Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age
    Type of Publication: Journal article published
    PubMed ID: 17395977
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  • 6
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0022-2836
    Keywords: HIV ; replication ; retrovirus ; reverse transcription ; termination
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2018-01-31
    Description: HIV-infected subjects under antiretroviral treatment (ART) harbor a persistent viral reservoir in resting CD4 + T cells, which accounts for the resurgence of HIV replication after ART interruption. A large majority of HIV reservoir genomes are genetically defective, but even among intact proviruses few seem able to generate infectious virus. To understand this phenomenon, we examined the function and expression of HIV envelope glycoproteins reactivated from the reservoir of four HIV-infected subjects under suppressive ART. We studied full-length genetically intact env sequences from both replicative viruses and cell-associated mRNAs. We found that these Env proteins varied extensively in fusogenicity and infectivity, with strongest functional defects found in Envs from cell-associated mRNAs. Env functional impairments were essentially explained by defects in Env protein expression. Our results support the idea that defects in HIV Env expression, preventing cytopathic or immune HIV clearance, contribute to the persistence of the HIV T-cell reservoir in vivo . IMPORTANCE In most individuals, evolution of HIV infection is efficiently controlled on the long-term by combination antiviral therapies. These treatments, however, fail to eradicate HIV from the infected subjects, a failure that results both in resurgence of virus replication and in resumption of HIV pathogenicity when the treatment is stopped. HIV resurgence, in these instances, is widely assumed to emerge from a reservoir of silent virus integrated in the genomes of a small number of T lymphocytes. The silent HIV reservoir is mostly composed of heavily deleted or mutated HIV DNA. Moreover, among the seemingly intact remaining HIV, only very few are actually able to efficiently propagate in tissue culture. In this study, we find that intact HIV in the reservoir often carry strong defects in their capacity to promote fusion to neighboring cells and infection of target cells, a defect related to the function and expression of the HIV envelope glycoprotein. Impaired envelope glycoprotein expression and function could explain why cells harboring these viruses tend to remain undetected and unharmed in the reservoir.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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