Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • COLON-CANCER  (32)
  • 1
    Keywords: CANCER ; SURVIVAL ; THERAPY ; BREAST-CANCER ; TRIALS ; colorectal cancer ; chemotherapy ; COLON-CANCER ; QUESTIONNAIRE ; MANAGEMENT ; UPDATE ; quality of life ; SURVIVORS ; ADJUVANT CHEMOTHERAPY ; OLDER ; CANCER SURVIVORS ; Long term
    Abstract: Purpose. To investigate the age-specific pattern of administration of chemotherapy and its association with long-term survival and quality of life (QoL) in stage II and III colorectal cancer patients. Methods. Chemotherapy allocation according to disease and patient characteristics was investigated in a population-based cohort of 562 stage II and III colorectal cancer patients. Five years after diagnosis, survival was determined and QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items and a tumor specific module. The association among chemotherapy, survival, and QoL was examined while controlling for potential confounders. Results. Chemotherapy was administered in 71% of patients aged 〈60 years and in only 20% of patients aged 〉/=80 years. A significant association between chemotherapy and longer survival time was found for stage III cancer only. Chemotherapy was associated with higher symptom levels for trouble with taste, anxiety, and hair loss. In age-specific analyses, younger survivors (〈70 years at time of follow-up) with a history of chemotherapy reported significantly lower physical, role, and cognitive functioning and higher pain, appetite loss, hair loss, and trouble with taste symptom levels. In contrast, for older survivors (〉/=70 years), only two (hair loss and dry mouth) out of 38 QoL scores were significantly associated with chemotherapy. Discussion. Chemotherapy is associated with lower long-term QoL, especially in younger survivors. In cases of uncertain survival benefits of chemotherapy, consideration of its long-term effects on QoL should be incorporated into final decisions on treatment.
    Type of Publication: Journal article published
    PubMed ID: 22101506
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    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
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: PROGRESSION ; FIBER ; COLON-CANCER ; ULCERATIVE-COLITIS ; METAANALYSIS ; RED MEAT ; MULTIETHNIC COHORT ; susceptibility loci ; ENVIRONMENT INTERACTION ; ASSOCIATION SCAN
    Abstract: Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.
    Type of Publication: Journal article published
    PubMed ID: 24743840
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    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
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: EXPRESSION ; mechanisms ; ASSOCIATION ; TRANSCRIPTIONAL ACTIVITY ; COLON-CANCER ; TESTOSTERONE ; ER-BETA ; HORMONE-THERAPY ; ESTROGEN-RECEPTOR-BETA ; ANDROGEN-RECEPTOR
    Abstract: Background: Evidence has accumulated which suggests that sex steroids influence colorectal cancer development and progression. We therefore assessed the association of repeat polymorphisms in the estrogen receptor beta gene (ESR2) and the androgen receptor gene (AR) with colorectal cancer risk and prognosis. Methods: The ESR2 CA and AR CAG repeat polymorphisms were genotyped in 1798 cases (746 female, 1052 male) and 1810 controls (732 female, 1078 male), matched for sex, age and county of residence. Colorectal cancer risk associations overall and specific for gender were evaluated using multivariate logistic regression models adjusted for sex, county of residence and age. Associations with overall and disease-specific survival were evaluated using Cox proportional hazard models adjusted for established prognostic factors (diagnosis of other cancer after colorectal cancer diagnosis, detection by screening, treatment with adjuvant chemotherapy, tumour extent, nodal status, distant metastasis, body mass index, age at diagnosis and year of diagnosis) and stratified for grade of differentiation. Heterogeneity in gender specific associations was assessed by comparing models with and without a multiplicative interaction term by means of a likelihood ratio test. Results: The average number of ESR2 CA repeats was associated with a small 5% increase in colorectal cancer risk (OR = 1.05, 95% CI 1.01-1.10) without significant heterogeneity according to gender or tumoural ESR2 expression. We found no indication for an association between the AR CAG repeat polymorphisms and risk of colorectal cancer. The ESR2 CA and AR CAG repeat polymorphisms were not associated with overall survival or disease specific survival after colorectal cancer diagnosis. Conclusions: Higher numbers of ESR2 CA repeats are potentially associated with a small increase in colorectal cancer risk. Our study does not support an association between colorectal cancer prognosis and the investigated repeat polymorphisms.
    Type of Publication: Journal article published
    PubMed ID: 25376484
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: COLON-CANCER ; microsatellite instability ; REPLICATION ; ISLAND METHYLATOR PHENOTYPE ; DNA-POLYMERASE-EPSILON
    Abstract: Recent molecular profiling studies reported a new class of ultramutated colorectal cancers (CRCs), which are caused by exonuclease domain mutations (EDMs) in DNA polymerase e (POLE). Data on the clinical implications of these findings as to whether these mutations define a unique CRC entity with distinct clinical outcome are lacking. We performed Sanger sequencing of the POLE exonuclease domain in 431 well-characterized patients with microsatellite stable (MSS) CRCs of a population-based patient cohort. Mutation data were analyzed for associations with major epidemiological, clinical, genetic, and pathological parameters including overall survival (OS) and disease-specific survival (DSS). In 373 of 431 MSS CRC, all exons of the exonuclease domain were analyzable. Fifty-four mutations were identified in 46 of these samples (12.3%). Besides already reported EDMs, we detected many new mutations in exons 13 and 14 (corresponding to amino acids 410-491) as well as in exon 9 and exon 11 (corresponding to aa 268-303 and aa 341-369). However, we did not see any significant associations of EDMs with clinicopathological parameters, including sex, age, tumor location and tumor stage, CIMP, KRAS, and BRAF mutations. While with a median follow-up time of 5.0 years, survival analysis of the whole cohort revealed nonsignificantly different adjusted hazard ratios (HRs) of 1.35 (95% CI: 0.82-2.25) and 1.44 (0.81-2.58) for OS and DSS indicating slightly impaired survival of patients with EDMs, subgroup analysis for patients with stage III/IV disease receiving chemotherapy revealed a statistically significantly increased adjusted HR (1.87; 95% CI: 1.02-3.44). In conclusion, POLE EDMs do not appear to define an entirely new clinically distinct disease entity in CRC but may have prognostic or predictive implications in CRC subgroups, whose significance remains to be investigated in future studies.
    Type of Publication: Journal article published
    PubMed ID: 25124163
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    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
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    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
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: COLON-CANCER ; microsatellite instability ; POPULATION-BASED SAMPLE ; ULCERATIVE-COLITIS ; CROHNS-DISEASE ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; ISLAND METHYLATOR PHENOTYPE ; MOLECULAR-FEATURES ; MAIT CELLS
    Abstract: We identified the minor allele (T) in SNP rs11676348 to have pleiotropic effect on risk of UC and CRC, particularly in tumors with an inflammatory component. Our findings offer the promise of risk stratification of UC patients for developing CRC.Although genome-wide association studies (GWAS) have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies. Among 11794 CRC cases and 14190 controls, rs11676348, the susceptibility single nucleotide polymorphism (SNP) for UC, was significantly associated with reduced risk of CRC (P = 7E-05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI 0.89-0.96). The association of the SNP with risk of CRC differed according to mucinous histological features (P (heterogeneity) = 0.008). In addition, the (T) allele was associated with lower risk of tumors with Crohn's-like reaction but not tumors without such immune infiltrate (P (heterogeneity) = 0.02) and microsatellite instability-high (MSI-high) but not microsatellite stable or MSI-low tumors (P (heterogeneity) = 0.03). The minor allele (T) in SNP rs11676348, located downstream from CXCR2 that has been implicated in CRC progression, is associated with a lower risk of CRC, particularly tumors with a mucinous component, Crohn's-like reaction and MSI-high. Our findings offer the promise of risk stratification of inflammatory bowel disease patients for complications such as CRC.
    Type of Publication: Journal article published
    PubMed ID: 26071399
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    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
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...