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  • HEALTH  (14)
  • 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: SURGERY ; RISK-FACTORS ; HEALTH ; CIGARETTE-SMOKING ; COMPLICATIONS ; LIFE-STYLE FACTORS ; ASSOCIATIONS ; INHIBITS APOPTOSIS ; PUBLICATION BIAS ; POSTOPERATIVE OUTCOMES
    Abstract: Smoking is a risk factor for colorectal cancer (CRC) incidence and mortality. However, little is known on smoking and its association with survival after CRC diagnosis. We conducted a systematic review and meta-analysis to summarize current evidence. A systematic literature search was carried out in MEDLINE and ISI Web of Science. We included studies that analyzed recurrence-free survival, disease-free survival, all-cause, and CRC-specific mortality according to smoking status. Data were extracted in duplicate. Standard methods of meta-analysis were applied. Sixteen studies from 11 countries were identified, comprising a total sample size of 62 278 CRC patients. Overall, in the 16 included studies, current smoking and, to a lesser extent, former smoking were rather consistently associated with a poorer prognosis compared with never smokers. Meta-analyses yielded random-effects hazard ratio estimates (95% confidence intervals) for all-cause mortality of 1.26 (1.15-1.37) and 1.11 (0.93-1.33) for current and former smokers, compared with never smokers, respectively. In particular, 30-day mortality was found to be increased by between 49% and 100% among current compared with never smokers. Our results support the existence of detrimental effects of smoking on survival also after CRC diagnosis. Perspectives for enhancing prognosis of CRC patients by smoking abstinence deserve increased attention in further research and clinical practice.
    Type of Publication: Journal article published
    PubMed ID: 24692581
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  • 3
    Keywords: DISEASE ; HEALTH ; DESIGN ; COLON-CANCER ; PANCREATIC-CANCER ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; RISK LOCI ; COMMON SNPS ; HUMAN HEIGHT
    Abstract: A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) associated with CRC risk. Although it has been shown that these CRC susceptibility SNPs only explain a small proportion of the genetic risk, it is not clear how much of the heritability these SNPs explain and how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we estimated the heritability of CRC under different scenarios using Genome-Wide Complex Trait Analysis in the Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases and 10 814 controls. We estimated that the heritability explained by known common CRC SNPs identified in GWAS was 0.65% (95% CI:0.3-1%; P = 1.11 x 10-16), whereas the heritability explained by all common SNPs was at least 7.42% (95% CI: 4.71-10.12%; P = 8.13 x 10(-8)), suggesting that many common variants associated with CRC risk remain to be detected. Comparing the heritability explained by the common variants with that from twin and family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In addition, our analysis showed that the gene x smoking interaction explained a significant proportion of the CRC variance (P = 1.26 x 10(-2)). In summary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified
    Type of Publication: Journal article published
    PubMed ID: 24562164
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  • 4
    Keywords: HEALTH ; PROSTATE-CANCER ; COLON-CANCER ; PREDICTION ; MUTATION CARRIERS ; METAANALYSIS ; GENOME-WIDE ASSOCIATION ; TASK-FORCE ; CHROMOSOME 8Q24 ; AMERICAN-COLLEGE
    Abstract: BACKGROUND & AIMS: Risk for colorectal cancer (CRC) can be greatly reduced through screening. To aid in the development of screening strategies, we refined models designed to determine risk of CRC by incorporating information from common genetic susceptibility loci. METHODS: By using data collected from more than 12,000 participants in 6 studies performed from 1990 through 2011 in the United States and Germany, we developed risk determination models based on sex, age, family history, genetic risk score (number of risk alleles carried at 27 validated common CRC susceptibility loci), and history of endoscopic examinations. The model was validated using data collected from approximately 1800 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, conducted from 1993 through 2001 in the United States. RESULTS: We identified a CRC genetic risk score that independently predicted which patients in the training set would develop CRC. Compared with determination of risk based only on family history, adding the genetic risk score increased the discriminatory accuracy from 0.51 to 0.59 (P = .0028) for men and from 0.52 to 0.56 (P = .14) for women. We calculated age-and sex-specific 10-year CRC absolute risk estimates based on the number of risk alleles, family history, and history of endoscopic examinations. A model that included a genetic risk score better determined the recommended starting age for screening in subjects with and without family histories of CRC. The starting age for high-risk men (family history of CRC and genetic risk score, 90%) was 42 years, and for low-risk men (no family history of CRC and genetic risk score, 10%) was 52 years. For men with no family history and a high genetic risk score (90%), the starting age would be 47 years; this is an intermediate value that is 5 years earlier than it would be for men with a genetic risk score of 10%. Similar trends were observed in women. CONCLUSIONS: By incorporating information on CRC risk alleles, we created a model to determine the risk for CRC more accurately. This model might be used to develop screening and prevention strategies.
    Type of Publication: Journal article published
    PubMed ID: 25683114
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  • 5
    Keywords: MORTALITY ; SURGERY ; RISK-FACTORS ; HEALTH ; CIGARETTE-SMOKING ; COLON-CANCER ; LIFE-STYLE ; METAANALYSIS ; CHEMOTHERAPEUTIC DRUGS ; INHIBITS APOPTOSIS
    Abstract: Current evidence on the association between smoking and colorectal cancer (CRC) prognosis after diagnosis is heterogeneous and few have investigated dose-response effects or outcomes other than overall survival. Therefore, the association of smoking status and intensity with several prognostic outcomes was evaluated in a large population-based cohort of CRC patients; 3,130 patients with incident CRC, diagnosed between 2003 and 2010, were interviewed on sociodemographic factors, smoking behavior, medication and comorbidities. Tumor characteristics were collected from medical records. Vital status, recurrence and cause of death were documented for a median follow-up time of 4.9 years. Using Cox proportional hazards regression, associations between smoking characteristics and overall, CRC-specific, non-CRC related, recurrence-free and disease-free survival were evaluated. Among stage I-III patients, being a smoker at diagnosis and smoking 15 cigarettes/day were associated with lower recurrence-free (adjusted hazard ratios (aHR): 1.29; 95% confidence interval (CI): 0.93-1.79 and aHR: 1.31; 95%-CI: 0.92-1.87) and disease-free survival (aHR: 1.26; 95%-CI: 0.95-1.67 and aHR: 1.29; 95%-CI: 0.94-1.77). Smoking was associated with decreased survival in stage I-III smokers with pack years 20 (Overall survival: aHR: 1.40; 95%-CI: 1.01-1.95), in colon cancer cases (Overall survival: aHR: 1.51; 95%-CI: 1.05-2.17) and men (Recurrence-free survival: aHR: 1.51; 95%-CI: 1.09-2.10; disease-free survival: aHR: 1.49; 95%-CI: 1.12-1.97), whereas no associations were seen among women, stage IV or rectal cancer patients. The observed patterns support the existence of adverse effects of smoking on CRC prognosis among nonmetastatic CRC patients. The potential to enhance prognosis of CRC patients by promotion of smoking cessation, embedded in tertiary prevention programs warrants careful evaluation in future investigations. What's new? Smoking is an established risk factor for a variety of cancers, including colorectal cancer, but evidence regarding its impact on the prognosis of colorectal cancer patients remains sparse. In this population-based study of 3,130 colorectal cancer patients, smoking was associated with reduced survival among patients with nonmetastatic colon cancer. The analyses suggested that the association may be more pronounced in men than women. Future studies should take into account relationships between smoking and other lifestyle factors and should explore the potential role of using the teachable moment of cancer diagnosis in the promotion of smoking cessation.
    Type of Publication: Journal article published
    PubMed ID: 25758762
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  • 6
    Keywords: HEALTH ; DESIGN ; CIGARETTE-SMOKING ; OBESITY ; COLON-CANCER ; microsatellite instability ; PHYSICAL-ACTIVITY ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; INSTRUMENTAL VARIABLES
    Abstract: Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer. Methods: Weused data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study-identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis. Results: Individuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk[ per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10-1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m(2), 1.50; 95% CI, 1.13-2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m(2), 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m(2), 1.18; 95% CI, 0.73-1.92). Conclusions: High BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation. Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer.
    Type of Publication: Journal article published
    PubMed ID: 25976416
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  • 7
    Keywords: CANCER ; COMBINATION ; Germany ; COHORT ; cohort study ; DISEASE ; POPULATION ; RISK ; DRUG ; IMPACT ; REDUCTION ; ASSOCIATION ; TRIAL ; TRIALS ; ADENOMAS ; prevention ; HEALTH ; colorectal cancer ; PROSPECTIVE COHORT ; COLORECTAL-CANCER ; COLON-CANCER ; POPULATIONS ; case-control studies ; aspirin ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; chemoprevention ; RANDOMIZED-TRIAL ; SINGLE ; ONCOLOGY ; case control study ; case-control study ; REGRESSION ; RE ; CARDIOVASCULAR-DISEASE ; METAANALYSIS ; case control studies ; INTERVAL ; USA ; prospective ; DRUGS ; odds ratio ; colorectal ; cardiovascular disease ; LONG-TERM USE ; LOGISTIC-REGRESSION ; statins
    Abstract: Recent research has drawn attention to protective effects of statins on colorectal cancer (CRC) and possible joint effects with other drugs. Because statins are often administered in combination With low-dose aspirin for the prevention of cardiovascular disease, the aim of our study was to investigate individual and combined effects of statins and low-dose aspirin on CRC risk. We assessed use of statins and low-dose aspirin in 540 cases with histologically confirmed incident CRC and 614 control subjects in a populations based case-control study in Germany. Multiple logistic regression. was used to estimate the impact of regular use of either low-dose aspirin or statins, and of both drugs combined on CRC risk. We found modest risk reduction of CRC for regular use of low-dose aspirin (adjusted odds ratio 0.77, 95% confidence interval 0.551.07) and a stronger association with regular use of statins (OR 0.65, 95% CI 0.43-0.99) or use of both drugs (OR 0.63, 95% CI 0.36-1.10). Combined use of low-dose aspirin and statins was associated with risk reduction by 62% after 5 or more years (OR 0.38, 95% CI 0.15-0.97). Combinational chemoprevention with low-dose aspirin and statins might provide stronger risk reduction than either of the single drugs after at least 5 years use, but confirmation is needed, preferably in prospective cohort studies and eventually by randomized controlled trials. (c) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17487832
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  • 8
    Keywords: CANCER ; Germany ; HISTORY ; MORTALITY ; RISK ; validation ; FAMILY ; REDUCTION ; NO ; prevention ; HEALTH ; AGE ; family history ; colorectal cancer ; COLORECTAL-CANCER ; EFFICACY ; cancer risk ; case-control studies ; aspirin ; sensitivity ; specificity ; VALIDITY ; SCREENING SIGMOIDOSCOPY ; case control study ; case-control study ; RE ; FAMILIES ; colonoscopy ; case control studies ; INTERVAL ; FAMILY-HISTORY ; USA ; reproducibility of results ; odds ratio ; CANCER-RISK ; colorectal neoplasms ; ENDOSCOPY ; colorectal ; POLYPECTOMY ; KAPPA ; mass screening ; MEDICAL-RECORD AUDIT ; reporting ; validation studies ; VETERANS
    Abstract: Large-bowel endoscopy with removal of polyps strongly reduces colorectal cancer risk. In epidemiologic studies, ascertainment of large-bowel endoscopies often relies on self-reports and might be prone to imperfect recall. In 2003-2004, the authors assessed the validity of self-reported colorectal endoscopies in a population-based case-control study including 540 cases and 614 controls from southwest Germany and calculated odds ratios of colorectal cancer risk according to self-reports and medical records. They sought to obtain all medical records for the last self-reported endoscopy and for a subsample of 100 subjects reporting no previous endoscopy. In total, 377 of 483 records could be obtained (78%). Sensitivity of self-reports was 100%, and specificity ranged from 93% to 98% among subgroups defined by age, gender, education, family history of colorectal cancer, and case-control status. The odds ratios for colorectal cancer risk after previous colonoscopy were 0.31 (95% confidence interval: 0.21, 0.45) using self-reports and 0.31 (95% confidence interval: 0.20, 0.47) using medical records. However, agreement between self-reports and medical records was poor regarding type of endoscopy (colonoscopy, sigmoicloscopy, or rectoscopy; kappa = 0.22), moderate concerning polypectomy (kappa = 0.58), and reasonable for year of examination (kappa = 0.70). Self-reports of previous colorectal endoscopies agreed well with medical records, but validation appears to be essential with respect to details of the examination
    Type of Publication: Journal article published
    PubMed ID: 17456475
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  • 9
    Keywords: CANCER ; Germany ; screening ; HISTORY ; incidence ; POPULATION ; RISK ; PATIENT ; FAMILY ; HEALTH ; DIFFERENCE ; AGE ; family history ; WOMEN ; meta-analysis ; colorectal cancer ; MEN ; COLORECTAL-CANCER ; COLON-CANCER ; UNITED-STATES ; RELATIVES ; INITIATION ; RELATIVE RISK ; GUIDELINES ; STATES ; REGISTRY ; review ; RE ; AGGREGATION ; FAMILIES ; aging ; cancer registries ; colonoscopy ; METAANALYSIS ; LEVEL ; methods ; cancer registry ; FAMILY-HISTORY ; PEOPLE ; RECOMMENDATIONS ; population-based ; ENGLAND ; LARGE-BOWEL-CANCER ; GRADIENT ; STATE
    Abstract: OBJECTIVES: To review and combine the best available epidemiological evidence, by sex and age, that may help decision and policy makers form recommendations as to how much earlier colorectal cancer (CRC) screening should be initiated among people with a family history of CRC than among average-risk people. PATIENTS AND METHODS: Combining population-based cancer registry and health interview survey data from the United States and results of a recent meta-analysis of epidemiological studies, we estimated cumulative incidence of CRC within subsequent 10 yr (Cl-10) at various ages among men and women with and without a family history of CRC. We estimated both the Cl-10 levels reached in average-risk 45-, 50-, 55-, and 60-yr-old men and women and the age at which the same Cl-10 levels are reached in men and women with a history of CRC in a first-degree relative. RESULTS: Despite major differences in CRC risk by sex, and despite the strong age gradient in relative risk associated with a positive family history, "risk advancement periods" for those with a family history were consistently found to be between 9 and 11 yr for both sexes and at all four ages assessed. CONCLUSION: Advancement of first CRC screening by 10 yr among both men and women with a family history of CRC compared to the average-risk population (e.g., from 50 to 40 yr of age) appears to be a reasonable, evidence-based recommendation
    Type of Publication: Journal article published
    PubMed ID: 18702651
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  • 10
    Keywords: CANCER ; COHORT ; RISK ; GENE ; RISK-FACTORS ; ASSOCIATION ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; HEALTH ; COLON-CANCER ; ALCOHOL ; CONSUMPTION ; FRUIT ; LIFE-STYLE ; MASS INDEX ; CANCER SUSCEPTIBILITY ; METAANALYSIS ; VEGETABLE CONSUMPTION ; LOCI ; GENOME-WIDE ASSOCIATION ; sex ; SCAN ; RISK LOCI ; CHROMOSOME 8Q24
    Abstract: Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal P-interaction = 1.3 x 10(-4); adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption.
    Type of Publication: Journal article published
    PubMed ID: 22367214
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