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  • 1
    Keywords: CANCER ; Germany ; DIAGNOSIS ; FOLLOW-UP ; HISTORY ; RISK ; REDUCTION ; colon ; cancer prevention ; prevention ; HEALTH ; AGE ; WOMEN ; colorectal cancer ; MEN ; COLORECTAL-CANCER ; COST-EFFECTIVENESS ; RANDOMIZED-TRIAL ; ONCOLOGY ; RE ; INCREASE ; LEVEL ; biomarker ; case control studies ; cancer research ; ENDOSCOPY ; FLEXIBLE SIGMOIDOSCOPY ; colorectal ; ASYMPTOMATIC ADULTS ; LINE FINDINGS ; POLYPECTOMY ; SCREENING TRIAL
    Abstract: We aimed to estimate the proportions of colorectal cancer cases that might be prevented by sigmoidoscopy compared with colonoscopy among women and men. In a population-based case control study conducted in Germany, 540 cases with a first diagnosis of primary colorectal cancer and 614 controls matched for age, sex, and county of residence were recruited. A detailed lifetime history of endoscopic examinations of the large bowel was obtained by standardized personal interviews, validated by medical records, and compared between cases and controls, paying particular attention to location of colorectal cancer and sex differences. Overall, 39%, 77%, and 64% of proximal, distal, and total colorectal cancer cases were estimated to be preventable by colonoscopy. The estimated proportion of total colorectal cancer cases preventable by sigmoidoscopy was 45% among both women and men, assuming that sigmoidoscopy reaches the junction of the descending and sigmoid colon only and findings of distal polyps are not followed by colonoscopy. Assuming that sigmoidoscopy reaches the splenic flexure and colonoscopy is done after detection of distal polyps, estimated proportions of total colorectal cancer preventable by sigmoidoscopy increase to 50% and 55% (73% and 91% of total colorectal cancer preventable by primary colonoscopy) among women and men, respectively. We conclude that colonoscopy provides strong protection against colorectal cancer among both women and men. The proportion of this protection achieved by sigmoidoscopy with follow-up colonoscopy in case of distal polyps may be larger than anticipated. Among men, this regimen may be almost as effective as colonoscopy, at least at previous performance levels of colonoscopy
    Type of Publication: Journal article published
    PubMed ID: 17337649
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  • 2
    Keywords: CANCER ; Germany ; INFORMATION ; EXPOSURE ; RISK ; GENE ; METABOLISM ; PATIENT ; HETEROCYCLIC AMINES ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY ; AGE ; CIGARETTE-SMOKING ; colorectal cancer ; smoking ; COLORECTAL-CANCER ; cancer risk ; genetic polymorphism ; CARCINOGENS ; case-control studies ; TOBACCO ; INDIVIDUALS ; CONSUMPTION ; meat ; ONCOLOGY ; case-control study ; REGRESSION ; RE ; ALLELE ; CARCINOGEN ; SUBSTRATE ; case control studies ; INTERVAL ; ENZYME ; analysis ; GENOTYPE ; MEAT CONSUMPTION ; USA ; odds ratio ; RISK-FACTOR ; CANCER-RISK ; colorectal ; LOGISTIC-REGRESSION ; N-ACETYLTRANSFERASE-1 ; NAT2 GENETIC POLYMORPHISMS ; SULFOTRANSFERASE 1A1 ; SULT1A1
    Abstract: Several procarcinogens that are present in cooked red meat and tobacco smoke are substrates for sulfotransferase 1A1 (SULT1A1). The association between environmental exposures and colorectal cancer risk may be modified by individual differences in the metabolism. Thus, we investigated the effect of a common polymorphism in the SULT1A1 gene associated with decreased enzyme activity on the susceptibility to colorectal cancer in a population-based case-control study. Patients (505) and 604 age- and sex-matched controls provided detailed risk factor information and were genotyped for SULT1A1 G638A using a fluorescence-based melting curve analysis method. Multivariate logistic regression analysis was used to estimate colorectal cancer risk associated with environmental exposures by SULT1A1 genotype. SULT1A1 genotype was not an independent risk factor for colorectal cancer. Risk of colorectal cancer associated with frequent consumption of red meat was significantly elevated among carriers of the SULT1A1*2 allele but not increased among subjects with the SULT1A1*1/*1 genotype (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.1 and OR 1.0, 95% CI 0.5-2.1, respectively). Colorectal cancer risk associated with 30+ pack-years of active smoking was higher among carriers of the SULT1A1*2 allele (OR 1.7, 95 % CI 1.0-3.2) than among individuals with the SULT1A1*1/*1 genotype (OR 1.1, 95% CI 0.6-2.1). Our results do not support a main effect of SULT1A1 genotype with regard to colorectal cancer but suggest that individuals with the low activity SULT1A1*2 allele may be at higher risk following carcinogen exposure than those with the SULT1A1*1/*1 genotype. (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17013894
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  • 3
    Keywords: RECEPTOR ; APOPTOSIS ; CANCER ; GROWTH ; GROWTH-FACTOR ; proliferation ; CELL ; CELL-PROLIFERATION ; Germany ; PATHWAY ; RISK ; SITE ; GENE ; GENES ; PROTEIN ; PROTEINS ; transcription ; DIFFERENTIATION ; SERA ; BINDING ; ASSOCIATION ; LINKAGE ; polymorphism ; POLYMORPHISMS ; BREAST-CANCER ; NO ; SNP ; colorectal cancer ; COLORECTAL-CANCER ; PROSTATE-CANCER ; REGION ; REGIONS ; LINKAGE DISEQUILIBRIUM ; case-control studies ; BINDS ; BINDING PROTEIN ; insulin ; CELL-GROWTH ; signaling ; SERUM ; SINGLE ; ONCOLOGY ; BINDING-PROTEIN ; case control study ; case-control study ; RE ; SNPs ; cell proliferation ; PROMOTER POLYMORPHISM ; GROWTH-FACTOR-I ; LEVEL ; case control studies ; methods ; HAPLOTYPE ; HAPLOTYPES ; single-nucleotide ; IGFBP3 ; SERUM-LEVELS ; HAPLOTYPE RECONSTRUCTION ; CIRCULATING LEVELS ; ENGLAND ; IGFBP-3 ; MULTIETHNIC COHORT ; colorectal ; case control ; UPSTREAM ; REPEAT ; IGF1 ; CASCADE ; GENETIC-VARIATION ; IGF ; INSULIN-LIKE ; cell growth ; BONE-MINERAL DENSITY ; INSULIN-LIKE-GROWTH-FACTOR-1
    Abstract: Background: The insulin-like growth factor1 (IGF1) pathway plays a significant role in both the normal and malignant cell growth. IGF1 binds to the IGF1 receptor and starts a signaling cascade that regulates cell proliferation, differentiation, and apoptosis. The bioavailability of IGF1 is regulated by the binding protein IGFBP3. A CA repeat polymorphism, in the IGF1 gene, which is located 969 bp upstream from the transcription start site and the rs2854744 and rs2854746 single nucleotide polyrnorphisms (SNPs) in the IGFBP3 gene have been associated with the serum levels of the respective proteins and colorectal cancer (CRC), but the results are inconsistent. We wanted to study if these polymorphisms or any haplotypes of the IGF1 and the IGFBP3 genes are associated with CRC. Methods: High linkage disequilibrium was seen in these gene regions. Therefore, the CA repeat along with two SNPs in the IGF1 gene, and rs2854744 (A-202C), rs2854746 (Ala32Gly) and two additional SNPs in the IGFBP3 gene were selected to cover the whole gene regions. A case-control study was carried out using 661 German CRC cases and 607 matched controls. Results: We did not find any association between the CA repeat length or any of the SNPs in the IGF1 and the IGFBP3 genes and the risk of CRC. Nor did the haplotypes of these genes affect the risk of CRC. Conclusion: Our study suggests no major role of the assessed genetic variation within the IGF1 and the IGFBP3 genes in CRC risk. (c) 2007 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18031946
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  • 4
    Keywords: APOPTOSIS ; CANCER ; proliferation ; CELL ; Germany ; EXPOSURE ; RISK ; RISKS ; GENE ; PROTEIN ; DRUG ; DIFFERENTIATION ; NF-KAPPA-B ; DNA ; GENETIC POLYMORPHISMS ; cell cycle ; CELL-CYCLE ; CYCLE ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; VARIANTS ; PROGRESSION ; DNA-REPAIR ; REPAIR ; genetics ; colorectal cancer ; COLORECTAL-CANCER ; p53 ; TUMOR-SUPPRESSOR GENE ; cancer risk ; GENOTYPES ; gene-environment interaction ; genetic polymorphism ; MULTIVARIATE ; CARRIERS ; case-control studies ; aspirin ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; heredity ; DNA repair ; ARREST ; case control study ; case-control study ; REGRESSION ; RE ; VARIANT ; ALLELE ; genomics ; interaction ; case control studies ; INTERVAL ; analysis ; methods ; GENOTYPE ; HAPLOTYPE ; HAPLOTYPES ; USA ; LINKAGE PHASE ; DRUGS ; odds ratio ; CANCER-RISK ; genomic ; microbiology ; colorectal ; LOGISTIC-REGRESSION ; FUNCTIONAL-ANALYSIS ; ANTIINFLAMMATORY DRUGS ; COLON ADENOCARCINOMA CELLS ; nonsteroidal anti-inflammatory drugs ; P53 POLYMORPHISMS ; SULINDAC SULFIDE ; TP53 gene
    Abstract: Objective Substantial evidence indicates that nonsteroidal anti-inflammatory drugs protect against colorectal cancer by altering cell cycle progression and/or inducing apoptosis, whereas p53 protein is crucial to maintaining cell-cycle arrest and regulating DNA repair, differentiation, and apoptosis. Genetic variants in TP53 gene might therefore influence colorectal cancer risk and modify the effects of nonsteroidal anti-inflammatory drugs. We assessed the association of TP53 Arg72Pro and p53PIN3 polymorphisms with colorectal cancer risk and their possible interaction with nonsteroidal antiinflammatory drug use. Methods We included 467 cases and 563 controls from a population-based case-control study. Multivariate logistic regression analysis was used to estimate the association between genotypes, environmental exposures and colorectal cancer risk, adjusting for potential confounders. Results Odds ratios of colorectal cancer were 0.75 (95% confidence interval, 0.57-0.99) for TP53 72Pro carriers compared with those homozygous for the TP53 72Arg allele and 0.78 (95% confidence interval, 0.58-1.05) for p53PIN3 A2 carriers compared with p53PIN3 A1A1. Risks differed by nonsteroidal anti -inf lam matory drug use. For both investigated TP53 polymorphisms, we found that the colorectal cancer risk associated with regular nonsteroidal anti-inflammatory drug use was statistically significantly modified by the TP53 genotype (P values for interaction=0.049 and 0.034, respectively), whereby a substantial protective effect of nonsteroidal antiinflammatory drug use was observed for homozygous carriers of the 72Arg allele and of the PIN3 Al allele (odds ratio 0.44; 95% confidence interval, 0.30-0.65 and odds ratio, 0.45; 95% confidence interval, 0.31-0.65). The interaction between nonsteroidal anti-inflammatory drugs and TP53 genetic polymorphisms was confirmed by haplotype analysis. Conclusions These data suggest that the TP53 genotype may modify the influence of nonsteroidal anti-inflammatory drug use on the risk of colorectal cancer. A direct proof of functional analysis is warranted to confirm these findings. Pharmacogenetics and Genomics 17:639-645 (C) 2007 Lippincott Williams & Wilkins
    Type of Publication: Journal article published
    PubMed ID: 17622940
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  • 5
    Keywords: CANCER ; Germany ; MODEL ; MODELS ; neoplasms ; INFORMATION ; screening ; COHORT ; POPULATION ; RISK ; DESIGN ; AGE ; WOMEN ; colorectal cancer ; MEN ; COLORECTAL-CANCER ; PREVALENCE ; REGRESSION ; PROGRAM ; aging ; colonoscopy ; METAANALYSIS ; BIRTH ; CANCER INCIDENCE ; colorectal neoplasms ; PARTICIPATION ; POLYPS ; COHORTS ; STRATIFICATION
    Abstract: BACKGROUND: Prevalence of advanced colorectal neoplasms increases with age and is higher among men than women. Cross-sectional analyses estimated that men reach an equivalent prevalence at a much younger age than women. However, cross-sectional estimates may be confounded by birth cohort effects. OBJECTIVE: To estimate age and cohort effects in advanced colorectal neoplasms and to adjust risk-advancement periods for men compared with women for birth cohort effects. DESIGN: Age-cohort analyses. SETTING: German screening colonoscopy program, 2003 to 2007. PARTICIPANTS: 2 185 153 participants aged 55 to 75 years. MEASUREMENTS: Sex- and age-specific prevalence of colorectal cancer (CRC) and advanced neoplasms (CRC or advanced adenoma) were plotted with and without stratification by birth cohort. Risk-advancement periods with 95% CI for men compared with women were estimated from log-binomial regression models with and without cross-sectional analysis adjustment for birth cohort effects. RESULTS: Overall, 17 196 participants (0.8%) had CRC and 152 429 (7.0%) had any advanced neoplasm. Age-specific prevalence was higher in men than in women and in later birth cohorts. The apparent modest increase in prevalence by age in cross-sectional analysis was much steeper after birth cohort effects were controlled for. In cross-sectional analysis, risk-advancement periods (95% CI) for men compared with women were 8.4 years (CI, 7.7 to 9.0 years) and 16.1 years (CI, 15.8 to 16.5 years) for CRC and any advanced neoplasm, respectively, and 3.4 years (CI, 2.6 to 4.3 years) and 6.9 years (CI, 6.4 to 7.4 years) after controlling for birth cohort effects. LIMITATION: Information on covariates that could explain cohort effects was lacking. CONCLUSION: In this population, strong cohort effects reduced age gradients in advanced colorectal neoplasms and inflated risk-advancement periods for men compared with women, but major risk advancement persisted, even after birth cohort effects were controlled for. Primary Funding Source: None.
    Type of Publication: Journal article published
    PubMed ID: 20513827
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  • 6
    Keywords: RISK ; COLORECTAL-CANCER
    Type of Publication: Journal article published
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  • 7
    Keywords: EXPRESSION ; POPULATION ; RISK ; GENOTYPES ; METAANALYSIS ; GENE POLYMORPHISMS ; VDR
    Abstract: Background: The vitamin D receptor (VDR) gene is present in colorectal cancer (CRC) cells and its genetic variants have been associated with an increased risk of CRC. The association with colorectal cancer prognosis remains widely unexplored. Methods: 1397 colorectal cancer patients participating in two cancer cohorts (ESTHER II and VERDI) and in a population-based case-control study (DACHS) were followed for 5 years. Unadjusted and adjusted hazard ratios for all-cause mortality (469 events) and CRC-specific mortality (336 events) were estimated for VDR variants rs731236 (TaqI), rs2228570 (FokI), rs11568820 (Cdx2), and rs1989969 (VDR-5132). Results: No association was found between VDR polymorphism and CRC specific and all-cause mortality. Adjusted hazard ratios ranged from 0.79 (95% CI 0.57-1.12) to 1.14 (95% CI 0.89-1.46) for CRC-specific mortality and from 0.89 (95% CI 0.67-1.18) to 1.22 (95% CI 0.99-1.50) for all-cause mortality. All 95% confidence intervals included the null value. Conclusions: Our findings do not support the hypothesis that the common VDR gene variants investigated in this study are of clinical relevance with respect to CRC prognosis.
    Type of Publication: Journal article published
    PubMed ID: 24075799
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  • 8
    Keywords: EPIDEMIOLOGY ; RISK ; OBESITY ; COLON-CANCER ; LIFE-STYLE FACTORS ; ASSOCIATIONS ; METAANALYSIS ; PROMOTER METHYLATION ; FATTY-ACID SYNTHASE ; MOLECULAR-FEATURES
    Abstract: BACKGROUND: Previous studies reported a positive association of body mass index (BMI) with microsatellite-stable (MSS) but not with microsatellite-instable (MSI-high) colorectal cancer. However, information from population-based studies conducted in representative age groups is so far limited. METHODS: We conducted a population-based case-control study (DACHS) in Southern Germany, including 1,215 patients with incident colorectal cancer and 1,891 matched controls with no upper age limit. Information on risk factors of colorectal cancer was obtained in standardized interviews. Microsatellite instability was analyzed using a mononucleotide marker panel. RESULTS: Median age among cases was 69 years, and 115 cases were classified MSI-high (9.5%). In multivariate analyses, BMI was positively associated with both risk of MSI-high colorectal cancer [per 5 kg/m(2): OR, 1.71; 95% confidence interval (CI), 1.35-2.17] and risk of MSS colorectal cancer (OR, 1.20; 95% CI, 1.07-1.33). The association with MSI-high colorectal cancer was limited to women (OR, 2.04; 95% CI, 1.50-2.77; P interaction = 0.02) and most pronounced among ever users of postmenopausal hormone replacement therapy (OR, 4.68; 95% CI, 2.36-9.30; P interaction = 0.01). In case-only analyses, BMI was more strongly associated with MSI-high colorectal cancer than with MSS colorectal cancer among women (OR, 1.84; 95% CI, 1.13-1.82; P interaction = 0.01). CONCLUSIONS: This population-based study confirms previous findings of increased risk of MSS colorectal cancer with obesity between both sexes and suggests that overweight and obesity may also be associated with increased risk of MSI-high colorectal cancer among women. IMPACT: These findings extend available data on the association of BMI and microsatellite instability in colorectal cancer and may suggest a link between overweight and obesity with sporadic MSI-high colorectal cancer in women.
    Type of Publication: Journal article published
    PubMed ID: 24127414
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  • 9
    Keywords: FOLLOW-UP ; RISK ; prevention ; UNITED-STATES ; FLEXIBLE SIGMOIDOSCOPY ; OCCULT BLOOD-TEST ; SIDED COLON-CANCER ; POPULATION-BASED-ANALYSIS ; LOWER ENDOSCOPY ; TELEMARK POLYP
    Abstract: Objectives To review, summarise, and compare the evidence for effectiveness of screening sigmoidoscopy and screening colonoscopy in the prevention of colorectal cancer occurrence and deaths. Design Systematic review and meta-analysis of randomised controlled trials and observational studies. Data sources PubMed, Embase, and Web of Science. Two investigators independently extracted characteristics and results of identified studies and performed standardised quality ratings. Eligibility criteria Randomised controlled trials and observational studies in English on the impact of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality in the general population at average risk. Results For screening sigmoidoscopy, four randomised controlled trials and 10 observational studies were identified that consistently found a major reduction in distal but not proximal colorectal cancer incidence and mortality. Summary estimates of reduction in distal colorectal cancer incidence and mortality were 31% (95% confidence intervals 26% to 37%) and 46% (33% to 57%) in intention to screen analysis, 42% (29% to 53%) and 61% (27% to 79%) in per protocol analysis of randomised controlled trials, and 64% (50% to 74%) and 66% (38% to 81%) in observational studies. For screening colonoscopy, evidence was restricted to six observational studies, the results of which suggest tentatively an even stronger reduction in distal colorectal cancer incidence and mortality, along with a significant reduction in mortality from cancer of the proximal colon. Indirect comparisons of results of observational studies on screening sigmoidoscopy and colonoscopy suggest a 40% to 60% lower risk of incident colorectal cancer and death from colorectal cancer after screening colonoscopy even though this incremental risk reduction was statistically significant for deaths from cancer of the proximal colon only. Conclusions Compelling and consistent evidence from randomised controlled trials and observational studies suggests that screening sigmoidoscopy and screening colonoscopy prevent most deaths from distal colorectal cancer. Observational studies suggest that colonoscopy compared with flexible sigmoidoscopy decreases mortality from cancer of the proximal colon. This added value should be examined in further research and weighed against the higher costs, discomfort, complication rates, capacities needed, and possible differences in compliance.
    Type of Publication: Journal article published
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  • 10
    Keywords: POPULATION ; RISK ; ADENOMAS ; COST-EFFECTIVENESS ; PARTICIPANTS ; RANDOMIZED CONTROLLED-TRIAL ; sigmoidoscopy ; OCCULT BLOOD-TESTS ; colonography ; NEGATIVE COLONOSCOPY
    Abstract: BACKGROUND: Colorectal cancer (CRC) is the second most common cancer among both men and women in Germany. Owing to its relatively slow growth, perspectives for effective early detection are much better than for other forms of cancer. AIM: To summarize the evidence on effectiveness and cost-effectiveness of CRC screening, and to provide an overview on the current state and perspectives for effective CRC screening. MATERIALS AND METHODS: Summary and critical review of evidence from randomized trials and observational epidemiological studies. RESULTS: A reduction in CRC mortality by offering annual fecal occult blood tests or once-only flexible sigmoidoscopy has been demonstrated in randomized trials. Novel fecal immunochemical tests for hemoglobin in stool have been shown to be more sensitive than traditional fecal occult blood tests and could substantially improve noninvasive CRC screening. Epidemiological studies suggest that the majority of CRC cases and deaths could be prevented by colonoscopy and removal of colorectal adenomas. However, adherence to screening offered outside organized screening programs is low. The National Cancer Plan recommends an organized CRC screening program in Germany. The law on the early detection of cancer from April 2013 has paved the way for its implementation. DISCUSSION: The great potential for CRC prevention by early detection has so far only been realized to a very limited extent in Germany. Introduction of an organized screening program and the offer of enhanced noninvasive screening tests could strongly enhance the utilization and effectiveness of CRC screening in Germany. The political frame has been set, and timely quality-assured implementation is required.
    Type of Publication: Journal article published
    PubMed ID: 24562704
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