Industrial foods have been associated with increased risks of several chronic conditions. We investigated the relationship between the degree of food processing and risks of Crohn's disease (CD) and ...ulcerative colitis (UC) in the European Prospective Investigation into Cancer and Nutrition cohort.
Analyses included 413,590 participants (68.6% women; mean baseline age, 51.7 y) from 8 European countries. Dietary data were collected at baseline from validated country-specific dietary questionnaires. Associations between proportions of unprocessed/minimally processed and ultraprocessed food intake and CD and UC risks were estimated using Cox models to obtain hazard ratios (HRs) and 95% CIs. Models were stratified by center, age, and sex, and adjusted for smoking status, body mass index, physical activity, energy intake, educational level, and alcohol consumption.
During a mean follow-up period of 13.2 years, 179 incident cases of CD and 431 incident cases of UC were identified. The risk of CD was lower in people consuming high proportions of unprocessed/minimally processed foods (adjusted HR for the highest vs lowest quartile: 0.57; 95% CI, 0.35-0.93; P trend < .01), particularly fruits and vegetables (adjusted HRs, 0.54; 95% CI, 0.34-0.87 and 0.55; 95% CI, 0.34-0.91, respectively). There was no association between unprocessed/minimally processed food intake and the risk of UC. No association was detected between ultraprocessed food consumption and CD or UC risks.
In the European Prospective Investigation into Cancer and Nutrition cohort, consumption of unprocessed/minimally processed foods was associated with a lower risk of CD. No association between UC risk and food processing was found.
KRAS mutational status has been shown to be a predictive biomarker of resistance to anti-EGFR monoclonal antibody (mAb) therapy in patients with metastatic colorectal cancer. We report the spectrum ...of KRAS mutation in 1506 patients with colorectal cancer and the identification and characterization of rare insertion mutations within the functional domain of KRAS. KRAS mutations are found in 44.5% (670/1506) of the patients. Two cases are found to harbor double mutations involving both codons 12 and 13. The frequencies of KRAS mutations at its codons 12, 13, 61, and 146 are 75.1%, 19.3%, 2.5%, and 2.7%, respectively. The most abundant mutation of codon 12 is G12D, followed by G12V and G12C while G13D is the predominant mutation in codon 13. Mutations in other codons are rare. The KRAS mutation rate is significantly higher in women (48%, 296/617) than in men (42.1%, 374/889, P = 0.023). Tumors on the right colon have a higher frequency of KRAS mutations than those on the left (57.3% vs. 40.4%, P < 0.0001). Two in-frame insertion mutations affect the phosphate-binding loop (codon 10-16) of KRAS are identified. One of them has never been reported before. Compared with wild-type protein, the insertion variants enhance the cellular accumulation of active RAS (RAS-GTP) and constitutively activate the downstream signaling pathway. NIH3T3 cells transfected with the insertion variants show enhanced anchorage-independent growth and in vivo tumorigenicity. Potentially these mutations contribute to primary resistance to anti-EGFR mAb therapy but the clinical implication requires further validation.
Background & Aims The risk of colorectal neoplasms among siblings of patients with advanced adenomas is not clear. We determined the prevalence of advanced adenomas in the siblings of patients with ...advanced adenomas and compared it with that of siblings of individuals without these lesions. Methods In a blinded, cross-sectional study, colonoscopies were performed (from 2010 through 2014), at 2 hospitals in Hong Kong on 200 asymptomatic siblings of patients with advanced adenomas (exposed; mean age, 58.2 ± 6.3 years; adenomas ≥10 mm, high-grade dysplasia, villous, or tubulovillous) and 400 age- and sex-matched siblings of subjects with normal findings from colonoscopies and no family history of colorectal cancer (unexposed; mean age, 58.1 ± 6 years). We recruited 1 sibling per family. The primary outcome was prevalence of advanced adenomas. Results Baseline demographics (ie, aspirin use, smoking, body mass index, and metabolic diseases) did not differ significantly between exposed and unexposed individuals. The prevalence of advanced adenoma was 11.5% among the exposed subjects and 2.5% among the unexposed subjects (matched odds ratio mOR = 6.05; 95% confidence interval CI: 2.74−13.36; P < .001). The prevalence of adenomas ≥10 mm was higher among exposed than unexposed siblings (10.5% vs 1.8%; mOR = 8.59; 95% CI: 3.44−21.45; P < .001), as was the prevalence of villous adenomas (5.5% vs 1.3% in unexposed; mOR = 6.28; 95% CI: 2.02−19.53; P = .001) and all colorectal adenomas (39.0% vs 19.0% in unexposed; mOR = 3.29; 95% CI: 2.16−5.03; P < .001). Two cancers were detected in exposed siblings and none in unexposed siblings. Conclusions In a cross-sectional study of subjects undergoing colonoscopy in Hong Kong, siblings of individuals with at least 1 advanced adenoma had a 6-fold increased odds of advanced adenoma compared with subjects who had a sibling with a screening colonoscopy with no identified neoplasia. ClinicalTrials.gov , Number: NCT01593098.
Abstract Multiple intracellular signaling pathways, such as Wnt/β-catenin signaling, epidermal growth factor receptor/Ras signaling, and p53 signaling are frequently dysregulated in colorectal ...cancer. Recent evidence also points to the involvement of signaling pathways in the developmental process, including Notch signaling, Hedgehog signaling, and Hippo signaling. Dysregulation of these signaling pathways contribute to the acquisition of malignant phenotypes, including unchecked cell cycle progression, evasion of apoptosis, induction of genetic instability, and enhanced invasiveness and metastasis. Understanding their relative importance and crosstalk will provide a rational basis for anticancer drug development.
Abstract
Background and Aims
We aimed to investigate the association between protein intake and risk of inflammatory bowel disease IBD in the European Prospective Investigation into Cancer and ...Nutrition.
Methods
A total of 413 593 participants from eight European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. Dietary data were calibrated to correct errors in measures related to each country-specific questionnaire. Associations between proteins total, animal, and vegetable or food sources of animal proteins, and IBD risk were estimated by Cox proportional hazard models.
Results
After a mean follow-up of 16 years, 177 patients with Crohn’s disease CD and 418 with ulcerative colitis UC, were identified. There was no association between total protein, animal protein, or vegetable protein intakes and CD or UC risks. Total meat and red meat intakes were associated with UC risk (hazard ratio HR for the 4th vs 1st quartile = 1.40, 95% confidence interval CI = 0.99-1.98, p-trend = 0.01; and 1.61, 95% CI = 1.10-2.36, p-trend = 0.007, respectively. There was no association between other food sources of animal protein processed meat, fish, shellfish, eggs, poultry and UC. We found no association between food sources of animal proteins and CD risk.
Conclusions
Meat and red meat consumptions are associated with higher risks of UC. These results support dietary counselling of low meat intake in people at high-risk of IBD.
Graphical Abstract
Graphical Abstract
Dysregulated microRNA (miRNA) expression was profiled through a miRNA array comparison between human colorectal cancer tumors and their adjacent normal tissues. Specifically, using laser capture ...micro-dissection, miR-133a was shown to be significantly downregulated in primary colorectal cancer specimens compared with matched adjacent normal tissue. Ectopic expression of miR-133a significantly suppressed colorectal cancer cell growth in vitro and in vivo. Cell-cycle analysis revealed that miR-133a induced a G0/G1-phase arrest, concomitant with the upregulation of the key G1-phase regulator p21(Cip1). We further revealed that miR-133a markedly increased p53 protein and induced p21(Cip1) transcription. Studies in silico revealed that the 3'UTR of the ring finger and FYVE-like domain containing E3-ubiquitin protein ligase (RFFL), which regulates p53 protein, contains an evolutionarily conserved miR-133a binding site. miR-133a repressed RFFL-3'UTR reporter activity and reduced RFFL protein levels, indicating that miR-133a directly bound to RFFL mRNA and inhibited RFFL translation. Moreover, miR-133a sensitized colon cancer cells to doxorubicin and oxaliplatin by enhancing apoptosis and inhibiting cell proliferation. These data add weight to the significance of miR-133a in the development of CRC.
miR-133a serves as a potential tumor suppressor upstream of p53 in colorectal cancer and may sensitize cells to therapeutics.
The incidence of ulcerative colitis (UC) in Asia is increasing but reports on its long-term course are few. We set out determine the incidence, prevalence, and survival rate of UC in the Chinese ...population and phenotypic stability by longitudinal follow-up.
A cohort of Chinese UC patients were followed up in a tertiary referral center in Hong Kong between 1985 and 2006. Clinical data were prospectively collected since 2001. Population statistics were obtained from the Census and Statistics Department of Hong Kong for the calculation of age-specific incidence, prevalence, and survival. The disease phenotypes at diagnosis and upon follow-up were documented.
A total of 172 patients (51.7% men) with a median age at diagnosis of 37.0 years (range: 12.0-85.0) were included. The cohort was observed for a total of 1,393 person-years with a median follow-up duration of 7.0 years (range: 0.5-22.0). The age-standardized incidence and prevalence rates of UC per 100,000 were 2.1 (95% confidence interval, CI: 1.1-3.7) and 26.5 (95% CI: 22.6-30.9), respectively, in 2006. The 10-year cumulative rate of proximal extension was 23.8%. Only one patient developed colorectal cancer during the observation period. The cumulative colectomy rates were 2.4% and 7.6% at 1 and 10 years of follow-up. Overall survival was similar to that expected (P=0.07).
The incidence of UC has increased sixfold in the past two decades in Hong Kong. The complication, colorectal cancer, and colectomy rates are low in Chinese patients but increase with duration of illness.
Lower urinary tract symptoms (LUTS) have a strong effect on socio-economic and individual quality of life. The aim of the present study was to investigate the prevalence of LUTS in an Asian ...population.
A telephone survey of individuals aged ≥40 years and of Chinese ethnicity was conducted. The survey included basic demographics, medical and health history, drinking habits, International Prostate Symptom Score, overactive bladder symptom score, Patient Health Questionnaire (PHQ-9) score, and Short Form (SF)-12v2 score.
From March to May 2017, 18 881 calls were made, of which 1543 fulfilled the inclusion criteria. In the end, 1000 successful respondents were recruited (302 men and 698 women). Age-adjusted prevalence of overactive bladder syndrome was 15.1%. The older the respondent, the more prevalent the storage symptoms and voiding symptoms (storage symptoms:
=0.434, P<0.001; voiding symptom:
=0.190, P<0.001). Presence of hypertension and diabetes were found to be significantly and positively correlated with storage and voiding symptoms. Storage and voiding symptoms were found to affect PHQ-9 scores (storage symptoms:
=0.257, P<0.001; voiding symptoms:
=0.275, P<0.001) and SF-12v2 scores (storage symptoms:
=0.467, P<0.001; voiding symptoms:
=0.335; P<0.001). Nocturia was the most prominent symptom among patients who sought medical help for their LUTS.
Lower urinary tract symptoms are common in Asian populations. Both storage and voiding symptoms have a negative impact on mental health and general well-being of individuals.
Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are ...limited. We investigated the association between prediagnostic intake of these foods and dietary calcium, and the subsequent development of Crohn's disease (CD) and ulcerative colitis (UC).
In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, and cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n = 110) or UC (n = 244) during follow-up were matched with 4 controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking.
Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI, 0.32-1.19, p trend = 0.19) and 0.63 (95% CI, 0.28-1.42, p trend = 0.23) for CD, and 0.80 (95% CI, 0.50-1.30, p trend = 0.40) and 0.81 (95% CI, 0.49-1.34, p trend = 0.60) for UC, respectively. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI, 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI, 0.49-1.47).
Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect.
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