Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 102
Filtrar
1.
Gut ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632709

RESUMO

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.

2.
Am J Epidemiol ; 190(2): 230-238, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33524116

RESUMO

People with Lynch syndrome (LS), who carry a pathogenic mutation in a DNA mismatch repair gene, have increased risks of colorectal cancer (CRC) and endometrial cancer (EC). A high reported variability in cancer risk suggests the existence of factors that modify cancer risk for persons with LS. We aimed to investigate the associations between height and CRC and EC risk for persons with LS using data from 2 large studies. Information on 1,115 men and 1,553 women with LS from the Colon Cancer Family Registry (1998-2007) and the GEOLynch Cohort Study (2006-2017) was harmonized. We used weighted Cox proportional hazards regression models with age on the time axis to estimate adjusted hazard ratios and 95% confidence intervals for each 5-cm increment in self-reported height. CRC was diagnosed in 947 persons during 65,369 person-years of observation, and 171 women were diagnosed with EC during 39,227 person-years. Height was not associated with CRC for either men (per 5-cm increment, hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.91, 1.11) or women (per 5-cm increment, HR = 1.01, 95% CI: 0.92, 1.11), nor was height associated with EC (per 5-cm increment, HR = 1.08, 95% CI: 0.94, 1.24). Hence, we observed no evidence for an association of height with either CRC or EC among persons with LS.


Assuntos
Estatura , Neoplasias Colorretais/epidemiologia , Neoplasias do Endométrio/epidemiologia , Adulto , Fatores Etários , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais
3.
Eur J Nutr ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544207

RESUMO

PURPOSE: Emerging evidence suggests that diet is linked to survival in colorectal cancer patients, although underlying mechanisms are not fully understood. The aim of this study was to evaluate whether dietary exposures are associated with metabolite concentrations in colorectal cancer patients. METHODS: Concentrations of 134 metabolites of the Biocrates AbsoluteIDQ p180 kit were quantified in plasma samples collected at diagnosis from 195 stage I-IV colorectal cancer patients. Food frequency questionnaires were used to calculate adherence to the World Cancer Research Fund (WCRF) dietary recommendations and the Dutch Healthy Diet (DHD15) index as well as to construct dietary patterns using Principal Component Analysis. Multivariable linear regression models were used to determine associations between dietary exposures and metabolite concentrations. All models were adjusted for age, sex, body mass index, smoking status, analytical batch, cancer stage, and multiple testing using false discovery rate. RESULTS: Participants had a mean (SD) age of 66 (9) years, were mostly men (60%), and mostly diagnosed with stage II and III cancer. For the dietary pattern analyses, Western, Carnivore, and Prudent patterns were identified. Better adherence to the WCRF dietary recommendations was associated with lower concentrations of ten phosphatidylcholines. Higher intake of the Carnivore pattern was associated with higher concentrations of two phosphatidylcholines. The DHD15-index, Western pattern, or Prudent pattern were not associated with metabolite concentrations. CONCLUSION: In the current study, the WCRF dietary score and the Carnivore pattern are associated with phosphatidylcholines. Future research should elucidate the potential relevance of phosphatidylcholine metabolism in the colorectal cancer continuum. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT03191110.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33531437

RESUMO

BACKGROUND: Whether changes in vitamin D (25(OH)D3) levels after colorectal cancer (CRC) diagnosis influence clinical outcomes is unclear. We investigated the association of trajectories of 25(OH)D3 levels with recurrence and all-cause mortality. METHODS: In total, 679 patients were included in our data-analyses. Trajectories of 25(OH)D3 levels were defined on vitamin D status at diagnosis, and at six months and two years after diagnosis. Observed trajectories of 25(OH)D3 levels were consistent deficient levels (20%), consistent sufficient levels (39%), increasing levels (20%) and a temporary drop in levels (13%). Associations of trajectories of 25(OH)D3 with recurrence and all-cause mortality were assessed using multivariable Cox proportional hazard regression models. RESULTS: During a follow-up time of 2.2 years for recurrence and 3.5 years for all-cause mortality, 31 and 65 events occurred, respectively. No statistically significant associations were observed for vitamin D trajectories and the risk of recurrence. Patients who were consistently sufficient compared to patients who were consistently deficient had a lower risk of all-cause mortality (HR 0.39 95%CI 0.21-0.73). The risk of all-cause mortality seems lower in patients with increasing levels or a temporary drop in levels (HR 0.54 95%CI 0.27-1.10 and HR 0.40 95%CI 0.17-0.93) relative to patients with consistent deficient levels. CONCLUSIONS: CRC patients following a trajectory characterized by sufficient levels of 25(OH)D3 two years after diagnosis all appeared to have a lower risk of all-cause mortality compared to patients having consistent deficient levels. IMPACT: Further studies should investigate how trajectories of 25(OH)D3 levels are associated with CRC recurrence.

5.
Clin Nutr ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33478795

RESUMO

BACKGROUND & AIMS: The inflammatory potential of the diet has been linked to colorectal cancer (CRC) development and mortality. However, it is unknown whether it is also associated with CRC recurrence. Therefore, the aim of this study was to investigate the associations between the inflammatory potential of the diet and plasma inflammation markers as well as recurrence and all-cause mortality in CRC patients. METHODS: Data of the Colorectal cancer, Observational, LONgitudinal (COLON) study, a prospective cohort study, was used. Dietary intake, assessed using a semi-quantitative food frequency questionnaire, was available for 1478 patients at diagnosis and for 1334 patients six months after diagnosis. Dietary intake data were used to calculate the adapted dietary inflammatory index (ADII). Data about cancer recurrence and all-cause mortality, were assessed through linkage with the Netherlands Cancer Registry and the Municipal Personal Records Database, respectively. The association between the ADII (continuous) and inflammation markers (Interleukin (IL)6, IL8, IL10, Tumor Necrosis Factor (TNF)α, high sensitivity C-reactive protein (hsCRP) and a summary inflammatory z-score), measured with a multiplex assay using electrochemiluminiscence detection, was assessed using quantile regression analyses. Restricted cubic splines (RCS) analyses and multivariable Cox proportional hazard models were used to explore the relationship between the ADII and CRC outcomes. RESULTS: During a median follow-up time of 3.2 years (Interquartile range (IQR) 2.0-4.1) for recurrence and 4.8 years (IQR 3.5-5.9) for all-cause mortality, 228 recurrences and 279 deaths occurred. A more pro-inflammatory diet at diagnosis as well as six months after diagnosis was associated with higher levels of TNFα, hsCRP and the summary inflammatory z-score. Results of RCS showed no relationship between the ADII and CRC outcomes at both time points. Also results of the Cox proportional hazard models showed no associations between the ADII at both time points and recurrence (HR (95%CI) 0.98 (0.94-1.04) & 0.96 (0.91-1.02) or all-cause mortality (HR (95%CI) 1.03 (0.98-1.07) & 1.00 (0.95-1.05)). CONCLUSION: Our study did not show an association between the ADII and recurrence and all-cause mortality in CRC patients. Further research should also take into account molecular tumor subtypes, as the effect of the inflammatory potential of the diet on cancer recurrence and mortality is more likely to be present in tumors with an inflammatory signature. CLINICAL TRIAL REGISTRY NUMBERS AND WEBSITE: The colon study: NCT03191110; clinical trials.gov.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33318029

RESUMO

BACKGROUND: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. METHODS: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). RESULTS: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively). CONCLUSIONS: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. IMPACT: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.

7.
JNCI Cancer Spectr ; 4(5): pkaa051, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33134831

RESUMO

Background: Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown. Methods: Circulating concentrations of folate, folic acid, and folate catabolites p-aminobenzoylglutamate and p-acetamidobenzoylglutamate were measured by liquid chromatography-tandem mass spectrometry at diagnosis in 2024 stage I-III colorectal cancer patients from European and US patient cohort studies. Multivariable-adjusted Cox proportional hazard models were used to assess associations between folate, folic acid, and folate catabolites concentrations with recurrence, overall survival, and disease-free survival. Results: No statistically significant associations were observed between folate, p-aminobenzoylglutamate, and p-acetamidobenzoylglutamate concentrations and recurrence, overall survival, and disease-free survival, with hazard ratios ranging from 0.92 to 1.16. The detection of folic acid in the circulation (yes or no) was not associated with any outcome. However, among patients with detectable folic acid concentrations (n = 296), a higher risk of recurrence was observed for each twofold increase in folic acid (hazard ratio = 1.31, 95% confidence interval = 1.02 to 1.58). No statistically significant associations were found between folic acid concentrations and overall and disease-free survival. Conclusions: Circulating folate and folate catabolite concentrations at colorectal cancer diagnosis were not associated with recurrence and survival. However, caution is warranted for high blood concentrations of folic acid because they may increase the risk of colorectal cancer recurrence.

8.
Cancer Epidemiol ; 69: 101809, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32947154

RESUMO

BACKGROUND: Persons with Lynch syndrome (LS) have an increased risk of developing colorectal tumors (CRTs). Adherence to diet quality indices associated with colorectal cancer (CRC) risk in the general population has not been studied before in LS. METHODS: Dietary habits of 490 participants with LS from a prospective cohort study was collected using a food frequency questionnaire. The Dutch Healthy Diet index 2015 (DHD15-index) and Dietary Approaches to Stop Hypertension (DASH) were used to score food-based diet quality. Diet quality scores were divided into tertiles where a higher tertile reflects a higher diet quality. Multivariable Cox proportional hazard regression models were used to estimate the association between the DHD15-index, DASH score and CRT risk. RESULTS: During a median follow-up time of 53.4 months, 210 participants (42.9%) developed CRTs. The DHD-index and DASH score were not associated with CRT risk; hazard ratios for highest vs. lowest tertile were 1.00 (95% Confidence Interval (CI): 0.67-1.48) and 1.11 (95% CI: 0.74-1.69), respectively. No linear trends across the DHD-index and DASH score tertiles were observed (P-trend = 0.97 and 0.83 respectively). CONCLUSION: In contrast to observations in the general population, no evidence for an association between the food-based DHD15-index or DASH score and CRT risk was observed in persons with LS. Further studies are needed investigating the association between diet quality and mechanisms leading to the development of LS-associated tumors.

9.
Am J Epidemiol ; 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32803246

RESUMO

Persons with Lynch syndrome (LS - carrying a pathogenic mutation in a DNA mismatch repair gene) have an increased colorectal cancer (CRC) and endometrial cancer (EC) risk. A high reported variability in cancer risk suggests the existence of factors that modify cancer risk for LS. We aimed to investigate the association between height and CRC and EC for persons with LS using two large studies. Information of 1,213 men and 1,636 women with LS from the Colon Cancer Family Registry (1998-2007) and the GEOLynch cohort study (2006-2017) was harmonized. We used weighted Cox proportional hazard regression models with age on the time-axis to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for each 5 cm increment in self-reported height. CRC was diagnosed in 947 persons during 65,369 person-years of observation and 171 women were diagnosed with EC during 39,227 person-years of observation. Height was not associated with CRC for men (HR 1.00 per 5 cm, 95%CI: 0.91, 1.11) or women (HR 1.01 per 5 cm, 95%CI: 0.92, 1.11). Nor was height associated with EC (HR 1.08 per 5 cm, 95%CI: 0.94, 1.24). Hence, we observed no evidence for an association of height with either CRC or EC for persons with LS.

10.
Am J Hum Genet ; 107(3): 432-444, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758450

RESUMO

Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.


Assuntos
Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Genoma Humano/genética , Medição de Risco , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Teorema de Bayes , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
11.
Fam Cancer ; 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770331

RESUMO

A cancer diagnosis is suggested to be associated with changes in dietary and lifestyle habits. Whether this applies to persons with familial cancer, such as Lynch syndrome (LS) is unknown. We investigated whether a colorectal neoplasm (CRN) diagnosis in persons with LS is associated with changes in dietary and lifestyle habits over time. We used data of confirmed LS mutation carriers from the GEOLynch study, a prospective cohort study. Information on dietary intake and lifestyle habits was collected with a validated semi-quantitative food frequency questionnaire and a general questionnaire administered at baseline (2006-2008) and follow-up (2012-2017). Participants' medical records were used to identify CRN diagnoses. Changes in dietary and lifestyle habits in the CRN and the no-CRN group were compared using multivariable linear regression models for continuous variables and cross-tables with percentage change at follow-up compared with baseline for categorical variables. Of the 324 included participants, 146 developed a CRN (CRN group) between baseline and follow-up, while 178 did not (no-CRN group). Smoking cessation was more often reported in the CRN than in the no-CRN group (41.4% vs. 35.0%). There were no differences in changes of energy intake, alcohol, red meat, processed meat, dairy, fruit, vegetables and dietary fiber consumption, BMI, physical activity and NSAID use. Apart from a potentially higher likelihood of smoking cessation, we found little evidence that a CRN diagnosis is associated with changes in lifestyle habits in persons with LS.

12.
Therap Adv Gastroenterol ; 13: 1756284820923922, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547638

RESUMO

Background: Calcitriol, the active form of vitamin D, may inhibit colorectal cancer (CRC) progression, which has been mechanistically linked to an attenuation of a pro-inflammatory state. The present study investigated the associations between circulating 25 hydroxy vitamin D3 (25(OH)D3) levels and inflammatory markers (IL10, IL8, IL6, TNFα and hsCRP) in the 2 years following CRC diagnosis. Methods: Circulating 25(OH)D3 levels and inflammatory markers were assessed at diagnosis, after 6, 12 and 24 months from 798 patients with sporadic CRC participating in two prospective cohort studies. Associations between 25(OH)D3 levels and individual inflammatory markers as well as a summary inflammatory z-score were assessed at each time point by multiple linear regression analyses. To assess the association between 25(OH)D3 and inflammatory markers over the course of 2 years, linear mixed model regression analyses were conducted. Results: Higher 25(OH)D3 levels were associated with lower IL6 levels at diagnosis, at 6 months after diagnosis and over the course of 2 years (ß -0.06, 95% CI -0.08 to -0.04). In addition, 25(OH)D3 levels were inversely associated with the summary inflammatory z-score at diagnosis and over the course of 2 years (ß -0.17, 95% CI -0.25 to -0.08). In addition, a significant inverse association between 25(OH)D3 levels and IL10 was found over the course of 2 years. Intra-individual analyses showed an inverse association between 25(OH)D3 and IL10, IL6 and TNFα. No statistically significant associations between 25(OH)D3 and IL8 and hsCRP levels were observed. Conclusions: Serum 25(OH)D3 levels were inversely associated with the summary inflammatory z-score and in particular with IL6 in the years following CRC diagnosis. This is of potential clinical relevance as IL6 has an important role in chronic inflammation and is also suggested to stimulate cancer progression. Further observational studies should investigate whether a possible 25(OH)D3-associated reduction of inflammatory mediators influences treatment efficacy and CRC recurrence.

13.
Cancer Epidemiol Biomarkers Prev ; 29(6): 1135-1144, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32245785

RESUMO

BACKGROUND: Vitamin D status may be an important determinant of health-related quality of life of colorectal cancer survivors. The current study investigated longitudinal associations between serum 25-hydroxyvitamin D3 (25OHD3) concentrations and quality of life in stage I-III colorectal cancer survivors up to 2 years after treatment. METHODS: Patients with colorectal cancer (n = 261) were included upon diagnosis. Home visits (including blood sampling) were performed at diagnosis and at 6 weeks, 6 months, 1 year, and 2 years after treatment. Serum 25OHD3 concentrations were measured using LC/MS-MS and adjusted for season. Validated questionnaires were used to assess global quality of life and cognitive functioning (EORTC-QLQ-C30), fatigue (EORTC-QLQ-C30 and Checklist Individual Strength, CIS), and depression and anxiety (Hospital Anxiety and Depression Scale). Statistical analyses were performed using linear mixed models and adjusted for sex, age, time since diagnosis, therapy, comorbidities, physical activity, and body mass index. RESULTS: At diagnosis, 45% of patients were vitamin D deficient (<50 nmol/L). After treatment, 25OHD3 concentrations increased on average with 3.1 nmol/L every 6 months. In confounder-adjusted models, 20 nmol/L increments in 25OHD3 were longitudinally associated with increased global quality of life [ß 2.9; 95% confidence interval (CI), 1.5-4.3] and reduced fatigue (EORTC-QLQ-C30 subscale: ß -3.5; 95% CI, -5.3 to -1.8 and CIS: ß -2.8; 95% CI, -4.7 to -0.9). Observed associations were present both within and between individuals over time. CONCLUSIONS: Higher concentrations of 25OHD3 were longitudinally associated with better global quality of life and less fatigue in colorectal cancer survivors. IMPACT: This study suggests that higher 25OHD3 concentrations may be beneficial for colorectal cancer survivors. Future intervention studies are needed to corroborate these findings.

14.
Am J Clin Nutr ; 111(5): 1007-1017, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32190892

RESUMO

BACKGROUND: Higher concentrations of 25-hydroxyvitamin D3 [25(OH)D3] at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in vitamin D metabolism. OBJECTIVES: We aimed to investigate 25(OH)D3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality. METHODS: The study population included 1169 newly diagnosed stage I-III CRC patients from 2 prospective cohorts. Associations between 25(OH)D3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another. RESULTS: Serum 25(OH)D3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 vs. Q1: 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. Q1: 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (≥50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (<50 nmol/L) and had a low magnesium intake. No interactions between calcium and vitamin D in relation to all-cause mortality were observed. CONCLUSIONS: Our findings suggest that the presence of an adequate status of 25(OH)D3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings. The COLON study was registered at clinicaltrials.gov as NCT03191110. The EnCoRe study was registered at trialregister.nl as NTR7099.


Assuntos
Calcifediol/sangue , Cálcio/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Magnésio/sangue , Idoso , Neoplasias Colorretais/patologia , Suplementos Nutricionais/análise , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Prospectivos , Vitamina D
15.
BMC Med Inform Decis Mak ; 20(1): 54, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164641

RESUMO

BACKGROUND: Many colorectal cancer (CRC) survivors experience persisting health problems post-treatment that compromise their health-related quality of life (HRQoL). Prediction models are useful tools for identifying survivors at risk of low HRQoL in the future and for taking preventive action. Therefore, we developed prediction models for CRC survivors to estimate the 1-year risk of low HRQoL in multiple domains. METHODS: In 1458 CRC survivors, seven HRQoL domains (EORTC QLQ-C30: global QoL; cognitive, emotional, physical, role, social functioning; fatigue) were measured prospectively at study baseline and 1 year later. For each HRQoL domain, scores at 1-year follow-up were dichotomized into low versus normal/high. Separate multivariable logistic prediction models including biopsychosocial predictors measured at baseline were developed for the seven HRQoL domains, and internally validated using bootstrapping. RESULTS: Average time since diagnosis was 5 years at study baseline. Prediction models included both non-modifiable predictors (age, sex, socio-economic status, time since diagnosis, tumor stage, chemotherapy, radiotherapy, stoma, micturition, chemotherapy-related, stoma-related and gastrointestinal complaints, comorbidities, social inhibition/negative affectivity, and working status) and modifiable predictors (body mass index, physical activity, smoking, meat consumption, anxiety/depression, pain, and baseline fatigue and HRQoL scores). Internally validated models showed good calibration and discrimination (AUCs: 0.83-0.93). CONCLUSIONS: The prediction models performed well for estimating 1-year risk of low HRQoL in seven domains. External validation is needed before models can be applied in practice.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Modelos Estatísticos , Qualidade de Vida , Idoso , Neoplasias Colorretais/fisiopatologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco
16.
Cancer Epidemiol Biomarkers Prev ; 29(5): 956-965, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32132148

RESUMO

BACKGROUND: The associations of abdominal skeletal muscle mass index (SMI), visceral and subcutaneous adipose tissue (VAT and SAT, respectively), and mortality among patients with stage I-III colorectal cancer may differ for men and women, but only few studies stratified their data into men and women. We investigated associations of abdominal SMI, VAT, and SAT with overall mortality among men and among women with stage I-III colorectal cancer. METHODS: SMI, VAT, and SAT were assessed from abdominal CT images for 1,998 patients with stage I-III colorectal cancer diagnosed between 2006 and 2015. Restricted cubic splines (RCS) were used to investigate associations of SMI, VAT, and SAT with overall mortality. RESULTS: Average age of the participants was 67.9 ± 10.6 years and 58% were men. During a median follow-up of 4.3 years, 546 (27%) patients died. Among men, the association of SMI and mortality was statistically significant in a nonlinear way in the RCS analyses, with lower SMI levels associated with higher mortality. SMI was not associated with mortality among women. SAT was associated with mortality in a nonlinear way for men and for women, with lower SAT levels being associated with higher mortality. VAT was not significantly associated with mortality in men or women. CONCLUSION: Associations of abdominal skeletal muscle mass with mortality among patients with colorectal cancer were not the same for men and for women. IMPACT: This study stresses the importance for more attention on sex-related differences in body composition and cancer outcomes.

17.
Br J Nutr ; 123(10): 1187-1200, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32019627

RESUMO

B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.

18.
J Steroid Biochem Mol Biol ; 199: 105577, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31917319

RESUMO

Vitamin D metabolites, including 25-hydroxyvitamin D3 (25(OH)D3), may inhibit colorectal cancer (CRC) progression. Here we investigated cross-sectional and longitudinal associations of demographic, lifestyle and clinical characteristics with 25(OH)D3 serum concentrations in CRC patients at diagnosis and six months later. In 1201 newly-diagnosed stage I-III CRC patients, 25(OH)D3 levels were analysed twice. Multivariable linear regression was used to assess demographic, lifestyle and clinical determinants of 25(OH)D3 levels at diagnosis and six months later. Linear mixed models were used to assess characteristics associated with changes in 25(OH)D3 levels over time. Results of our study showed that vitamin D intake from diet or supplements, use of calcium supplements, BMI and disease stage were associated with 25(OH)D3 levels at both time points. Six months after diagnosis, gender and having received chemo- and/or radiotherapy were also associated with 25(OH)D3 levels. A stronger decrease in 25(OH)D3 levels was observed in patients who underwent chemotherapy, compared to surgery only (ß-6.9 nmol/L 95 %CI -9.8; -4.0). Levels of 25(OH)D3 levels increased in patients using vitamin D supplements compared to non-users (ß 4.0 nmol/L 95 %CI 1.2; 6.8). In conclusion, vitamin D supplement use and treatment appear to be important determinants of 25(OH)D3 levels during the first six months after CRC diagnosis, although the difference in 25(OH)D3 levels was minor. ClinicalTrials.gov Identifier: NCT03191110.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/análogos & derivados , Vitamina D/sangue , Idoso , Índice de Massa Corporal , Cálcio/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Suplementos Nutricionais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/patologia
20.
Nutr Cancer ; 72(3): 451-459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31298929

RESUMO

Objective: Chronic Chemotherapy-Induced Peripheral Neuropathy (CIPN) is highly prevalent among colorectal cancer (CRC) patients. Ergothioneine (ET) - a dietary antioxidant -protected against CIPN in experimental models, but human studies are lacking. We explored whether whole blood ET levels were associated with chronic peripheral neuropathy among CRC patients who had completed chemotherapy.Methods: At diagnosis, median ET-concentration in whole blood of 159 CRC patients was 10.2 µg/ml (7.2-15.8). Patients completed questionnaires on peripheral neuropathy 6 months after completion of chemotherapy. We calculated prevalence ratios (PR) to assess associations of ET-concentrations and prevalence of peripheral neuropathy and used linear regression to assess associations with severity of peripheral neuropathy.Results: Prevalence of total and sensory peripheral neuropathy were both 81%. Higher ET-concentrations tended to be associated with lower prevalence of total and sensory peripheral neuropathy, but not statistically significant (highest versus lowest tertile of ET: PR = 0.93(0.78, 1.11) for total neuropathy, and PR = 0.84(0.70, 1.02) for sensory neuropathy). ET-concentrations were not associated with severity of neuropathy.Conclusion: Statistically significant associations were not observed, possibly because of limited sample size. Although data may putatively suggest higher levels of ET to be associated with a lower prevalence of neuropathy, analyses should be repeated in larger populations with larger variability in ET-concentrations.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA