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1.
Anticancer Res ; 40(1): 101-107, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892558

RESUMO

BACKGROUND: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer. MATERIALS AND METHODS: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer. The mtDNA mutations in the non-neoplastic mucosa, tumor tissues, and healthy controls were compared. RESULTS: The incidence of mutations of nicotinamide adenine dinucleotide phosphate ubiquinone oxidase subunit, ATP synthetase, and tRNA was higher in non-neoplastic mucosa in those with UC compared with the healthy controls. However, no statistically significant differences were observed in mutations between the tumor tissues and non-neoplastic mucosa in UC. CONCLUSION: Significant mutations in mtDNA were observed in the non-neoplastic mucosa of patients with UC-associated cancer.


Assuntos
Colite Ulcerativa/complicações , Colite Ulcerativa/genética , Neoplasias Colorretais/etiologia , Genes Mitocondriais , Polimorfismo Genético , Transformação Celular Neoplásica/genética , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Suscetibilidade a Doenças , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Mutação
2.
Medicine (Baltimore) ; 99(1): e18530, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895788

RESUMO

The role of atopic dermatitis (AD) in the development of colorectal cancer (CRC) has been a matter of scientific debate with mixed results. We conducted a nationwide cohort study to assess the association between AD and risk of CRC. Drawing on Taiwan's National Health Insurance Research Database, 46,703 patients with AD (the AD cohort) and 186,812 sex, age, and index year-matched patients without AD (the non-AD cohort) were identified in the period between 2000 and 2008. Follow-up time was calculated from the date of entry in the cohort until the occurrence of a first CRC diagnosis, death, or the end of the observation period (December 31, 2013), whichever occurred first. Hazards ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Fine-Gray competing risk model were used to estimate the association between AD and CRC risk. After multivariable adjustment, AD was associated with an increased risk of CRC (adjusted HR, 1.26; 95% CI, 1.14-1.40). Of note, a significant positive association between AD and CRC risk was evident in both men and women and in all age groups. In summary, this population-based cohort study revealed that AD was associated with an increased risk of CRC in an Asian population. It will be of interest for cohort studies with prediagnostic specimens to evaluate the potential relationship between AD and CRC using biomarkers for allergy status.


Assuntos
Neoplasias Colorretais/epidemiologia , Dermatite Atópica/complicações , Adulto , Neoplasias Colorretais/etiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Adulto Jovem
3.
Medicine (Baltimore) ; 99(1): e18575, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895803

RESUMO

This was a meta-analysis of epidemiological articles that aimed to estimate the association of garlic intake with the risk of colorectal cancer (CRC).Electronic databases, including the Cochrane Database of Systematic Reviews, PubMed, and EMBASE, were systemically searched from inception to May 2019 to identify related articles. In addition, a random model was used to pool the included evidence based on heterogeneity. Additionally, subgroup analyses were carried out to examine the differences between different groups. The stability of our findings was tested through sensitivity analyses. Publication bias was also assessed by Egger and Begg tests. Moreover, all enrolled studies were ordered according to the publication year for a cumulative meta-analysis.A total of 11 studies (involving 12,558 cases) were included in the current meta-analysis. Our integrated relative risk (RR) of CRC was 0.80 (95% confidence interval [CI], 0.69-0.91) for the highest versus the lowest garlic consumption categories (RR: 0.71 [95% CI, 0.60-0.84] for controls and RR: 0.99 [95% CI, 0.80-1.23] for cohorts). There was significant heterogeneity across all enrolled studies (I = 68.3%, P < .01). The sensitivity analysis revealed no notable alterations of the integrated results. According to the funnel plot regarding garlic intake and the risk of CRC, together with the Egger test (P = .1) and Begg test (P = .064) results, there was no notable evidence of publication bias. The cumulative meta-analysis suggested that the 95% CIs became narrower with the increase in sample size.Based on the existing evidence, garlic intake could reduce the risk of CRC.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Alho , Adulto , Idoso , Ingestão de Alimentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
4.
Int J Cancer ; 146(3): 861-873, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31037736

RESUMO

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.


Assuntos
Neoplasias Colorretais/etiologia , Etanol/efeitos adversos , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de Risco
5.
Int J Cancer ; 146(3): 627-634, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30868574

RESUMO

Early detection of colorectal neoplasms can reduce the disease burden of colorectal cancer by timely intervention of individuals at high risk. Our aim was to evaluate a joint environmental-genetic risk score as a risk stratification tool for early detection of advanced colorectal neoplasm (ACRN). Known environmental risk factors and high-risk genetic loci were summarized into risk scores for ACRN in 1014 eligible participants of a screening study. The performances of single and joint environmental-genetic scores were evaluated with estimates and 95% confidence intervals (CI) of the absolute risk, relative risk and predictive ability using the area under the curve (AUC). Individuals with higher environmental risk scores showed increasing ACRN risk, with 3.1-fold for intermediate risk and 4.8-fold for very high risk, compared to the very low environmental risk group. Similarly, individuals with higher genetic risk scores showed increasing ACRN risk, with 2.2-fold for intermediate risk and 3.5-fold for very high risk, compared to the lowest genetic risk group. Moreover, the joint environmental-genetic score improved the ACRN risk stratification and showed higher predictive values (AUC = 0.64; 95%CI = 0.60-0.67) with substantial difference (p = 0.0002) compared to the single environmental score (0.58; 0.55-0.62). The integration of environmental and genetic factors looks promising for improving targeting individuals at high-risk of colorectal neoplasm. Applications in practical screening programs require optimization with additional genetic and other biomarkers involved in colorectal carcinogenesis.


Assuntos
Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Fatores Etários , Idoso , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etiologia , Feminino , Loci Gênicos/genética , Predisposição Genética para Doença , Alemanha/epidemiologia , Humanos , Estilo de Vida , Masculino , Anamnese , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco/métodos , Fatores de Risco
6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(12): 1216-1220, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874542

RESUMO

Colorectal carcinoma (CRC) is the third most common malignancy in adults. Pediatric colorectal carcinoma (PCRC) is a rare non-embryonal tumor with a significantly lower incidence compared to adults. The clinical manifestations of PCRC are not typical, and pediatricians usually have no enough experience in diagnosis and treatment. Therefore, early diagnosis is extremely difficult, which would always lead to late clinical stages when diagnosis is made. At present, the pathogenesis of PCRC is still not clear, and many countries have started to carry out researches at the level of genes, molecules and cells. In both tumor primary tumors and distant metastases, PCRC has obvious difference in distribution from adults, and the proportion of pathological type of mucous adenocarcinoma (including the signet ring cell carcinoma) was significantly higher than that of adults. Although treated according to adult colorectal cancer guidelines, PCRC has been unable to achieve ideal efficacy with poor prognosis and lower long-term survival rate. The purpose of this paper is to summarize the epidemiological characteristics, pathogenesis, clinical symptoms, pathological types, treatment and prognosis of colorectal cancer in children by reviewing the latest literatures at home and abroad.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/etiologia , Adenocarcinoma Mucinoso/terapia , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/epidemiologia , Carcinoma de Células em Anel de Sinete/etiologia , Carcinoma de Células em Anel de Sinete/terapia , Criança , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Humanos , Prognóstico
7.
Dis Colon Rectum ; 62(12): 1494-1504, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31725582

RESUMO

BACKGROUND: Primary sclerosing cholangitis is a classical extraintestinal manifestation in patients with ulcerative colitis. However, the impact of primary sclerosing cholangitis on the disease course is incompletely understood. OBJECTIVE: This study aimed to assess the impact of primary sclerosing cholangitis on disease phenotype and its course in patients with ulcerative colitis. DESIGN: This is a retrospective study with 3:1 matched cohorts. SETTINGS: Tertiary care center's electronic database was used for data analysis from 2000 and 2018. PATIENTS: Of 782 patients with ulcerative colitis, 77 patients who had coincident primary sclerosing cholangitis were included. MAIN OUTCOME MEASURES: The primary outcomes evaluated were disease characteristics including colonic disease activity, temporal change of disease course, colorectal neoplasia, and colectomy rates. RESULTS: Disease activity during acute flares, assessed by the complete Mayo score, was significantly lower in patients with primary sclerosing cholangitis (6.2 vs 7.3; p < 0.001). In addition, disease activity in patients with primary sclerosing cholangitis was decreased, especially within the first 10 years after disease onset, and biological therapy with anti-tumor necrosis factor and anti-integrin agents was commenced less frequently (22% vs 35%; p = 0.043) and later (10-year risk: 17.4% vs 27.8%; p = 0.034). Patients with primary sclerosing cholangitis were younger at colitis diagnosis (23.3 vs 29.3 years; p < 0.001) and had more extensive disease (75% vs 46%; p < 0.001). Colorectal cancer was more frequently detected in patients with coincident primary sclerosing cholangitis (6/77 vs 16/705; p = 0.016). Colectomy rates did not differ between both groups (14.3% vs 14.5%; p = 0.56). In contrast, patients with ulcerative colitis had to undergo surgery more frequently because of therapy-refractant inflammation, whereas surgery due to neoplasia development was increased in patients with coincident primary sclerosing cholangitis (p = 0.013). LIMITATIONS: The study was limited by its retrospective design. CONCLUSION: Patients who have ulcerative colitis with coincident primary sclerosing cholangitis develop a distinct disease course characterized by an earlier disease onset and lower disease activity, but more frequent extensive disease manifestation and higher risk for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B45. FENOTIPO DE ENFERMEDAD DISTINTIVO DE LA COLITIS ULCERATIVA EN PACIENTES CON COLANGITIS ESCLEROSANTE PRIMARIA CONCOMITANTE: EVIDENCIA DE UN ESTUDIO RETROSPECTIVO GRANDE CON COHORTES EMPAREJADAS: La colangitis esclerosante primaria es una manifestación extraintestinal clásica en pacientes con colitis ulcerativa. Sin embargo, el impacto de la colangitis esclerosante primaria en el curso de la enfermedad no es comprendido completamente.Evaluar el impacto de la colangitis esclerosante primaria en el fenotipo y curso de la enfermedad en pacientes con colitis ulcerativa.Este es un estudio retrospectivo con cohortes emparejadas 3:1.La base de datos electrónica de un centro de atención terciaria se utilizó para el análisis de datos de 2000 a 2018.782 pacientes con colitis ulcerativa, 77 padecían colangitis esclerosante primaria concomitante y fueron incluidos.Se evaluaron las características de la enfermedad, incluida la actividad de enfermedad colónica, el cambio temporal del curso de la enfermedad, la neoplasia colorrectal y las tasas de colectomía.La actividad de la enfermedad durante los brotes agudos, evaluada por la puntuación completa de Mayo, fue significativamente menor en pacientes con colangitis esclerosante primaria (6.2 vs 7.3; p < 0.001). Además, la actividad de la enfermedad en pacientes con colangitis esclerosante primaria se redujo especialmente en los primeros 10 años después del inicio de la enfermedad, y la terapia biológica con agentes anti-TNF y anti-integrina se inició con menos frecuencia (22% vs 35%; p = 0.043) y más tarde (riesgo a 10 años: 17.4% vs 27.8%; p = 0.034). Los pacientes con colangitis esclerosante primaria eran más jóvenes en el momento del diagnóstico de colitis (23.3 vs 29.3 años; p < 0.001) y tenían enfermedad más extensa (75% vs 46%; p < 0.001). El cáncer colorrectal se detectó con mayor frecuencia en pacientes con colangitis esclerosante primaria concomitante (6/77 vs 16/705; p = 0.016). Las tasas de colectomía no fueron diferentes entre ambos grupos (14.3% vs 14.5%; p = 0.56). En contraste, los pacientes con colitis ulcerativa tuvieron que someterse a cirugía con mayor frecuencia debido a inflamación refractaria a la terapia, mientras que el desarrollo de neoplasia se incrementó en pacientes con colangitis esclerosante primaria concomitante (p = 0.013).El estudio estuvo limitado por su diseño retrospectivo.Los pacientes con colitis ulcerativa con colangitis esclerosante primaria concomitante desarrollan un curso de enfermedad distintivo caracterizado por un inicio temprano de la enfermedad y una menor actividad de la enfermedad, pero con manifestación de enfermedad extensa más frecuente y un mayor riesgo de cáncer colorrectal. Vea el resumen en video en http://links.lww.com/DCR/B45.


Assuntos
Colangite Esclerosante/epidemiologia , Colectomia/estatística & dados numéricos , Colite Ulcerativa/patologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Adolescente , Adulto , Colangite Esclerosante/patologia , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Neoplasias Colorretais/etiologia , Comorbidade , Progressão da Doença , Feminino , Humanos , Masculino , Fenótipo , Estudos Retrospectivos , Tamanho da Amostra , Índice de Gravidade de Doença , Atenção Terciária à Saúde , Adulto Jovem
8.
Life Sci ; 238: 116968, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31628914

RESUMO

AIMS: Colorectal cancer (CRC) is the third most common cancer worldwide. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of many cytoprotective genes, plays a protective role in carcinogenesis. Recent studies have identified a specific gene-expression signature regulated by the Nrf2 pathway in lung adenocarcinoma and head-and-neck squamous cell cancer. However, the roles of Nrf2 in the development of colitis-associated colorectal cancer (CACC) have not been well characterized. Nrf2 target genes as prognostic biomarkers in CACC remain to be explored. Thus, this work aimed to identify the molecular changes that occur during mouse CACC progression to facilitate the development of diagnostic and prognostic biomarkers. MAIN METHODS: The CACC model was established using azoxymethane (AOM) with dextran sulfate sodium salt (DSS) in BALB/c mice for 3 weeks to induce colitis-associated adenoma (CAA, early stage) and for 9 weeks to induce colitis-associated carcinoma (CAC, late stage). Using RNA-sequencing and bioinformatics analyses we examined the mRNA expression profiles of 6 groups: wild-type control (WT-C), WT-CAA, WT-CAC, Nrf2 knockout control (Nrf2KO-C), Nrf2KO-CAA, and Nrf2KO-CAC. KEY FINDINGS: In the AOM/DSS model of colitis-associated tumorigenesis, Nrf2-/- mice showed a phenotype similar to WT mice, but with significantly more tumors and a much higher percentage of adenocarcinomas. We identified 47 novel Nrf2 genes via gene expression profiling of tumor samples. Survival analysis showed that 23 of these genes were biomarkers of a poor prognosis in colon cancer patients. SIGNIFICANCE: Nrf2 target genes deserve exploration as prognostic and therapeutic targets for CRC.


Assuntos
Biomarcadores/metabolismo , Carcinogênese/patologia , Colite/complicações , Neoplasias Colorretais/diagnóstico , Regulação Neoplásica da Expressão Gênica , Fator 2 Relacionado a NF-E2/fisiologia , Animais , Azoximetano/toxicidade , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinógenos/toxicidade , Colite/induzido quimicamente , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
9.
Nat Commun ; 10(1): 4614, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601814

RESUMO

Autophagy is a central component of integrated stress responses that influences many inflammatory diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). While the core machinery is known, the molecular basis of the epigenetic regulation of autophagy and its role in colon inflammation remain largely undefined. Here, we report that BRG1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for the homeostatic maintenance of intestinal epithelial cells (IECs) to prevent the inflammation and tumorigenesis. BRG1 emerges as a key regulator that directly governs the transcription of Atg16l1, Ambra1, Atg7 and Wipi2, which are important for autophagosome biogenesis. Defective autophagy in BRG1-deficient IECs results in excess reactive oxygen species (ROS), which leads to the defects in barrier integrity. Together, our results establish that BRG1 may represent an autophagy checkpoint that is pathogenetically linked to colitis and is therefore likely a potential therapeutic target for disease intervention.


Assuntos
Autofagia/fisiologia , Colite/etiologia , Neoplasias Colorretais/etiologia , DNA Helicases/genética , Doenças Inflamatórias Intestinais/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Animais , Estudos de Casos e Controles , Colite/complicações , Colite/patologia , Neoplasias Colorretais/genética , DNA Helicases/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica , Humanos , Doenças Inflamatórias Intestinais/patologia , Camundongos Knockout , Proteínas Nucleares/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/metabolismo
10.
Medicine (Baltimore) ; 98(38): e17076, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567943

RESUMO

Although accumulated epidemiological evidence indicates that a good physical fitness level may prevent the development of sporadic colorectal cancer (CRC), few studies have examined the effect of physical fitness level on familial adenomatous polyposis (FAP). This cross-sectional study aimed to examine the relationship between physical fitness and CRC development in patients with FAP.A total of 119 patients (54 male; 65 female) with FAP, aged 17 to 73 years, underwent a step test to induce exercise stress. Predicted maximal oxygen uptake (VO2max) was calculated for each patient by using heart rate as an index of physical fitness. The association of VO2max with the presence or absence of CRC and polyp diameter was examined. Patients with FAP were divided into 3 categories according to their VO2max (high, medium, and low). The association between maximum polyp size and VO2max among the patients with FAP without a history of colectomy was examined.The risk of CRC was significantly higher in the low VO2max group than in the high VO2max group (odds ratio = 4.07; 95% confidence interval, 1.02-16.26). The maximum polyp diameter was significantly negatively correlated with the VO2max among the patients with FAP without a history of colectomy (r = -.44, P = .01). In the multiple linear regression analysis, maximum polyp diameter was independently correlated with VO2max.Our results suggest a preventive association between physical fitness and CRC development or colorectal adenoma growth exists in patients with FAP.


Assuntos
Adenoma/prevenção & controle , Polipose Adenomatosa do Colo/complicações , Neoplasias Colorretais/prevenção & controle , Aptidão Física , Adenoma/etiologia , Adolescente , Adulto , Idoso , Neoplasias Colorretais/etiologia , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
11.
Medicine (Baltimore) ; 98(42): e17570, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626124

RESUMO

Perineural invasion (PNI) is a prognostic factor in patients with colorectal cancer. Neurotrophic factors, molecular determinants of PNI, are altered in their expression levels in patients with ulcerative colitis. In this study, we evaluated the frequency of PNI in colitis-associated cancer (CAC) and sporadic cancer.We retrospectively reviewed 778 colorectal cancers with pathological T3-T4 in 761 patients all of whom were surgically resected without preoperative treatment. The lesions were classified into either CAC or sporadic cancer based on the clinical information. Clinicopathological findings including PNI were compared between CACs and sporadic cancers. Moreover, we analyzed the risk factors for positive PNI by multivariate analysis using a logistic regression model.Ten of the cancers (1.3%) were diagnosed as CACs, and the remaining 768 as sporadic cancers. CACs were characterized by being nonobstructive and predominantly located in the rectum. The CACs had a larger size and more frequent undifferentiated histology than sporadic cancers. PNI was observed more frequently in CACs (90%) than in sporadic cancers without obstruction (45%, P = .007). On multivariate analysis, CAC was one of the significant factors associated with PNI (odds ratio: 9.05, P = .040).Our results suggest that CAC was more likely to exhibit PNI than sporadic colorectal cancer.


Assuntos
Adenocarcinoma/patologia , Colite Ulcerativa/complicações , Neoplasias Colorretais/patologia , Estadiamento de Neoplasias , Neoplasias do Sistema Nervoso Periférico/patologia , Reto/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Adulto , Idoso , Colite Ulcerativa/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias do Sistema Nervoso Periférico/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
12.
Rev Lat Am Enfermagem ; 27: e3195, 2019 Oct 14.
Artigo em Português, Inglês, Espanhol | MEDLINE | ID: mdl-31618388

RESUMO

OBJECTIVE: to identify the association between environmental risk factors and awareness of colorectal cancer in people at familial risk. METHOD: cross-sectional correlational study, with a sample consisted of people who met at least one of the Revised Bethesda criteria, and 80 participants were included in this study. A sociodemographic data record, the AUDIT Test for alcohol use, the Fagerström Test for tobacco smoking, the Estimation and Frequency of Food Intake scale, and the Cancer Awareness Measure questionnaire to assess the colorectal cancer awareness were used. Body mass index was calculated, and descriptive statistics and the Pearson's Correlation Coefficient were used to estimate the association. RESULTS: female sex predominated, with an average age of 37.8 years, almost half of the participants were overweight, 45% showed symptoms of alcohol dependence, half of the sample showed an association between hereditary factors and the development of colorectal cancer, and less than half of them were aware of cancer prevention programs. CONCLUSION: there is little information on the main environmental risk factors, signs and symptoms of colorectal cancer, and no significant association was found between these and colorectal cancer awareness.


Assuntos
Neoplasias Colorretais/etiologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Transtornos Induzidos por Álcool/complicações , Conscientização , Índice de Massa Corporal , Estudos Transversais , Dieta/efeitos adversos , Feminino , Predisposição Genética para Doença/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Fumar Tabaco/efeitos adversos , Adulto Jovem
13.
Anticancer Res ; 39(9): 4673-4679, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519566

RESUMO

BACKGROUND/AIM: Rats of the adenomatous polyposis coli (Apc)-mutated female polyposis in rat (PIRC) (F344/NTac-Apcam1137) model exhibit a low level of intestinal tumorigenesis and are thus potentially exploitable as a model for identifying substances increasing colorectal cancer (CRC). MATERIALS AND METHODS: To test this possibility, we treated such rats with the bile acid (BA) cholic acid (CA) (0.3% w/w in the diet), known to promote CRC, and assessed tumorigenesis. RESULTS: Precancerous colonic lesions (mucin-depleted foci) and intestinal tumors were dramatically increased in CA-treated rats compared to controls (p<0.01). Colon mucosa proliferation was higher and apoptosis lower than those in controls. Expression of nuclear receptor 1h4 (Nr1h4) gene [encoding for BA receptor farnesoid X receptor (FXR)], organic solute transporter beta (Ostb) and fatty acid-binding protein 6 (Fabp6), FXR-dependent BA transporters, were dramatically down-regulated in CA-treated rats. CONCLUSION: CA-increased tumorigenesis in female PIRC rats, with mechanisms involving increased proliferation, reduced apoptosis and marked down-regulation of genes controlling BA homeostasis. Since BAs have been implicated in CRC, we suggest that female PIRC rats can be used to identify CRC-promoting agents.


Assuntos
Transformação Celular Neoplásica/induzido quimicamente , Ácido Cólico/efeitos adversos , Neoplasias Colorretais/etiologia , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Animais , Apoptose/genética , Proliferação de Células , Modelos Animais de Doenças , Feminino , Expressão Gênica , Genes APC , Mutação , Lesões Pré-Cancerosas , Ratos
14.
Anticancer Res ; 39(9): 4877-4884, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519590

RESUMO

BACKGROUND/AIM: We investigated the effect of aspirin on colorectal cancer (CRC) risk among subgroups of women with and without risk factors for CRC. PATIENTS AND METHODS: Using data from the Women's Health Initiative, we estimated hazard ratios for CRC in association with aspirin use, with stratifications by cardiovascular disease (CVD) risk status, family history of CRC, and history of colorectal polypectomy. RESULTS: Aspirin was associated with a lower risk of CRC among women with low/normal or high CVD-risk status; no family history of CRC; or a history of colonoscopy with polypectomy. Aspirin was not associated with CRC among women with a family history of CRC or a history of colonoscopy without polypectomy. CONCLUSION: Aspirin was associated with a lower risk of CRC in women at all levels of CVD-risk, in those with a history of colonoscopy with polypectomy, and in those without a family history of CRC.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
15.
Nat Rev Gastroenterol Hepatol ; 16(11): 690-704, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31554963

RESUMO

Colorectal cancer (CRC) accounts for about 10% of all new cancer cases globally. Located at close proximity to the colorectal epithelium, the gut microbiota comprises a large population of microorganisms that interact with host cells to regulate many physiological processes, such as energy harvest, metabolism and immune response. Sequencing studies have revealed microbial compositional and ecological changes in patients with CRC, whereas functional studies in animal models have pinpointed the roles of several bacteria in colorectal carcinogenesis, including Fusobacterium nucleatum and certain strains of Escherichia coli and Bacteroides fragilis. These findings give new opportunities to take advantage of our knowledge on the gut microbiota for clinical applications, such as gut microbiota analysis as screening, prognostic or predictive biomarkers, or modulating microorganisms to prevent cancer, augment therapies and reduce adverse effects of treatment. This Review aims to provide an overview and discussion of the gut microbiota in colorectal neoplasia, including relevant mechanisms in microbiota-related carcinogenesis, the potential of utilizing the microbiota as CRC biomarkers, and the prospect for modulating the microbiota for CRC prevention or treatment. These scientific findings will pave the way to clinically translate the use of gut microbiota for CRC in the near future.


Assuntos
Neoplasias Colorretais/microbiologia , Microbioma Gastrointestinal , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/terapia , Progressão da Doença , Humanos
16.
Rev Med Liege ; 74(9): 479-483, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31486319

RESUMO

Lynch syndrome is a hereditary predisposition to several cancers. The goals of our study were to know the different mutations in our Lynch population, to evaluate the prevalence of cancers in this population and to determine the mean age of onset of those cancers. This retrospective study includes proven carriers of a MMR mutation diagnosed either by the CHU of Liège or either by the CHC Saint-Joseph in Liège, Belgium. We noted a clear majority of MSH2 mutations (50 %) in the Lynch families recorded in Liège, which is different from the main literature. In our study population (106 subjects), 65 % of subjects were affected by at least one cancer. Prevalences for colorectal and endometrial cancers are, respectively, 50 % and 27.5 %. We found no difference in the mean age of onset of cancers compared to literature. We discuss the follow-up of Lynch patients and the interest of additional exams such as hysteroscopy and cystoscopy.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Neoplasias do Endométrio , Predisposição Genética para Doença , Bélgica , Neoplasias Colorretais/etiologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias do Endométrio/etiologia , Feminino , Humanos , Mutação , Estudos Retrospectivos
17.
J. coloproctol. (Rio J., Impr.) ; 39(3): 217-222, June-Sept. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040327

RESUMO

ABSTRACT Background and study aims: Colorectal cancer (CRC) is the most common gastrointestinal cancer and the third most commonly diagnosed malignancy affecting about one million individuals each year. The etiology for most cases of CRC appears to be related to environmental factors. This study to describe the main characteristics of this malignancy regarding age, gender, and anatomical sub site distribution, as well as the main presenting symptoms in Iraqi patients. Patients and methods: Patients with newly-diagnosed CRC by colonoscopy findings and confirmed by histopathological examination of endoscopic colonic biopsies were studied. Results: Sixty three cases with a newly-diagnosed CRC were included in this study. There were 31 (49.2%) males and 32 (50.8%) females. CRC peaked in the 60-69 years old age group (p < 0.05), more than 60% were between 40 and 69 years old. Fresh bleeding per rectum was the most common symptom occurred in 48 (76.2%) patients; while the least common was weight loss (19%). The mean duration of symptoms before referral was 7.3 ± 12.6 months. The tumor sites of the CRC were the rectum and sigmoid region seen in 77.8% (p < 0.05), the rectum alone reported in 37 patients (58.7%); followed by sigmoid colon in 12 (19%) patients, cecum in 7 (11.1%) patients and the ascending colon seen in 2 (3.2%) patients. Conclusions: In this study CRC occurs in relatively younger age groups in comparison to studies in the developed countries with rectal cancer predominates of all colorectal cancers.


RESUMO Contexto e objetivos do estudo: O câncer colorretal é a neoplasia gastrointestinal mais comum e o terceiro tumor maligno mais comumente diagnosticado, afetando cerca de um milhão de pessoas anualmente. A etiologia da maioria dos casos de câncer colorretal parece estar relacionada a fatores ambientais. Este estudo descreve as principais características dessa neoplasia quanto à idade, gênero e distribuição anatômica do subsite, bem como os principais sintomas observados em pacientes iraquianos. Pacientes e métodos: O estudo avaliou pacientes com câncer colorretal recém-diagnosticado por achados de colonoscopia e confirmados por exame histopatológico de biópsias endoscópicas do cólon. Resultados: O estudo incluiu 63 casos de pacientes com câncer colorretal recém-diagnosticado; 31 (49,2%) homens e 32 (50,8%) mulheres. O câncer colorretal atingiu o pico na faixa etária de 60 a 69 anos (p < 0,05); mais de 60% dos pacientes tinham entre 40 e 69 anos de idade. O sangramento retal fresco foi o sintoma mais comum em 48 (76,2%) pacientes; o sintoma menos comum foi a perda de peso (19%). A duração média dos sintomas antes do encaminhamento para especialista foi de 7,3 ± 12,6 meses. Os principais sítios tumorais do câncer colorretal foram a região do reto e sigmoide em 77,8% dos pacientes (p < 0,05) e o reto isolado em 37 pacientes (58,7%); seguido por cólon sigmoide em 12 pacientes (19%), ceco em sete (11,1%) e cólon ascendente em dois pacientes (3,2%). Conclusões: No presente estudo, o câncer colorretal foi observado em grupos etários relativamente mais jovens do que em estudos conduzidos em países desenvolvidos; a neoplasia retal foi o tipo de câncer colorretal mais comumente observado.


Assuntos
Humanos , Masculino , Feminino , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/patologia , Sinais e Sintomas , Colonoscopia
18.
J Cancer Res Clin Oncol ; 145(9): 2169-2197, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31401674

RESUMO

BACKGROUND: Recent studies have shown that the short-chain fatty acids (SCFAs) produced by the gut microbiota play a positive role in the development of colorectal cancer (CRC). AIMS: This study aims to elucidate the "food-microorganism-SCFAs" axis and to provide guidance for prevention and intervention in CRC. METHODS: The PubMed, Embase and Cochrane databases were searched from their inceptions to August 2018, and 75 articles and 25 conference abstracts were included and analysed after identification and screening. RESULTS: The concentrations of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. The protective mechanism of SCFAs against CRC has been described in three aspects: epigenetics, immunology and molecular signalling pathways. Many food and plant extracts that were fermented by microorganisms produced SCFAs that play positive roles with preventive and therapeutic effects on CRC. The "food-microorganism-SCFAs" axis was constructed by summarizing the pertinent literature. CONCLUSIONS: This study provides insight into the basic research and practical application of SCFAs by assessing the protective effect of SCFAs on CRC.


Assuntos
Neoplasias Colorretais/prevenção & controle , Ácidos Graxos Voláteis/fisiologia , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/fisiologia , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/microbiologia , Ácidos Graxos Voláteis/uso terapêutico , Alimentos , Humanos , Padrões de Prática Médica/tendências , Probióticos/uso terapêutico , Fatores de Risco , Transdução de Sinais/fisiologia
20.
Klin Onkol ; 32(4): 261-269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31426641

RESUMO

BACKGROUND: The clinical, histopathological, and molecular characteristics of colorectal cancer vary considerably. Factors associated with the heterogeneity of this disease and with understanding the effects of heterogeneity on disease progression and response to therapy are critical for the better stratification of patients and the development of new therapeutic methods. Although studies have focused mainly on tumor molecular profiling, current molecular predictive and prognostic factors are relevant to specific groups of colorectal cancer patients and are mostly used to predict the applicability of targeted biological agents rather than to predict their benefits. Molecular profiling fails to capture aspects important for tumor growth and aggressiveness, including the tumor microenvironment. The gut microbiome, consisting of specific communities of all commensal, symbiotic, and pathogenic microorganisms, has been shown to have a significant impact on the development of many diseases, including Crohns disease, type II diabetes, and obesity. Recent studies have indicated that long-term dysbiosis of the intestinal microflora can influence the development and progression of colorectal cancer, as well as tumor aggressiveness and response to treatment. CONCLUSION: This review article summarizes current knowledge of the gut microbiome in colorectal cancer, including the various mechanisms by which the gut microbiome affects the intestinal wall, thereby contributing to the development and progression of colorectal cancer. This work was supported by Ministry of Health of the Czech Republic (project AZV 16-31966A), project of Ministry of Education, Youth and Sports of the Czech Republic - NPU I - LO1413 a Ministry of Health of the Czech Republic - RVO (MMCI, 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 15. 4. 2019 Accepted: 17. 6. 2019.


Assuntos
Neoplasias Colorretais/etiologia , Microbioma Gastrointestinal/fisiologia , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Disbiose/complicações , Disbiose/microbiologia , Humanos
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