Association of cigarette smoking with risk of colorectal cancer subtypes classified by gut microbiota.

INTRODUCTION: Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis. METHODS: A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes. RESULTS: Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend <0.05) but not for type I tumors. The associations of smoking with increased odds of colorectal neoplasm significantly differed by gut microbiota enterotypes (p<0.05 for heterogeneity). An increase in carcinogenic bacteria (genus Escherichia shigella) and a decrease in probiotics (family Lachnospiraceae and Ruminococcaceae) in type II tumors may drive disease progression by upregulating oncogenic signaling pathways and inflammatory/oxidative stress response pathways, as well as protein phospholipase D1/2, cytochrome C, and prostaglandin-endoperoxide synthase 2 expression. CONCLUSIONS: Smoking was associated with a higher odds of type II colorectal neoplasms but not type I tumors, supporting a potential role for the gut microbiota in mediating the association between smoking and colorectal neoplasms.

Gut Microbiota Enterotypes Mediate the Effects of Dietary Patterns on Colorectal Neoplasm Risk in a Chinese Population.

Colorectal cancer (CRC) risk is influenced by dietary patterns and gut microbiota enterotypes. However, the interaction between these factors remains unclear. This study examines this relationship, hypothesizing that different diets may affect colorectal tumor risk in individuals with varied gut microbiota enterotypes. We conducted a case-control study involving 410 Han Chinese individuals, using exploratory structural equation modeling to identify two dietary patterns, and a Dirichlet multinomial mixture model to classify 250 colorectal neoplasm cases into three gut microbiota enterotypes. We assessed the association between dietary patterns and the risk of each tumor subtype using logistic regression analysis. We found that a healthy diet, rich in vegetables, fruits, milk, and yogurt, lowers CRC risk, particularly in individuals with type I (dominated by Bacteroides and Lachnoclostridium) and type II (dominated by Bacteroides and Faecalibacterium) gut microbiota enterotypes, with adjusted odds ratios (ORs) of 0.66 (95% confidence interval [CI] = 0.48-0.89) and 0.42 (95% CI = 0.29-0.62), respectively. Fruit consumption was the main contributor to this protective effect. No association was found between a healthy dietary pattern and colorectal adenoma risk or between a high-fat diet and colorectal neoplasm risk. Different CRC subtypes associated with gut microbiota enterotypes displayed unique microbial compositions and functions. Our study suggests that specific gut microbiota enterotypes can modulate the effects of diet on CRC risk, offering new perspectives on the relationship between diet, gut microbiota, and colorectal neoplasm risk.

Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention.

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

Overexpression of YKL-40 Predicts Poor Prognosis in Patients Undergoing Curative Resection of Pancreatic Cancer.

OBJECTIVES: The aim of this study was to determine the prognostic value of YKL-40 expression in patients undergoing curative resection of pancreatic cancer. METHODS: This cohort study included 234 consecutive patients with pancreatic ductal adenocarcinoma who underwent curative resection. Surgical specimens were immunohistochemically assessed for YKL-40 expression. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of YKL-40 expression. A multivariate logistic regression model was performed to examine the correlation between YKL-40 expression and tumor stage. RESULTS: Of the 234 patients, YKL-40 overexpression was detected in 149 (63.7%) patients. Survival curves showed that patients with YKL-40 overexpression had significantly shorter survival time than those with low YKL-40 expression (P < 0.001). Cox regression analysis indicated that YKL-40 expression was an independent prognostic factor for both overall survival (hazard ratio, 3.82; 95% confidence interval [CI], 2.38-6.13) and progression-free survival (hazard ratio, 3.73; 95% CI, 2.33-5.99). Multivariate logistic regression analysis demonstrated that YKL-40 overexpression was an independent predictor for advanced tumor stage (odds ratio 4.15; 95% CI, 1.35-12.71). CONCLUSIONS: YKL-40 overexpression predicts poor prognosis and advanced tumor stage in patients undergoing curative resection of pancreatic cancer. Application of adjuvant treatment targeting the YKL-40 pathway may improve prognosis.

[The derivation and validation of a prediction rule for differential diagnosis of thyroid nodules].

OBJECTIVE: To set up a prediction rule for the pro-operative differential diagnosis of thyroid nodules and evaluate its clinical value. METHODS: All patients of thyroid nodules underwent thyroid operations in Changzheng hospital from June, 1997 to July, 2012 were included in this study. They were randomly divided into the derivation cohort (2/3) and the validation cohort (1/3). A prediction rule was developed based on the logistic regression model and the scoring system was established in accordance with assigning of the value of each variable ß in the model. The prediction consistency, discriminatory power and diagnostic accuracy were conducted to evaluate the clinical value of the scoring system. RESULTS: A total of 13 980 patients were enrolled in the study with 9195 in the derivation cohort and 4785 in the validation cohort. The prediction rule consisted of 18 variables, which were gender, clinical manifestations including fever, neck sore, neck mass, palpitation and sweating, serum level of thyroid stimulating hormone (TSH) , free triiodothyronine (FT3) , thyroid peroxidase antibody (TPOAb) , thyroglobulin antibody (TgAb) , thyroglobulin (Tg) , calcitonin and carcinoembryonic antigen (CEA) , ultrasonography features including nodules number, location, size, boundaries and ethological patterns and the presence and patterns of lymph nodes. The model showed good calibration consistency (P = 0.437) and discrimination power (area under the receiver operating characteristic curve was 0.928) in the derivation cohort. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the model were 89.3%, 81.5%, 83.2%, 56.8%, 96.6%, 4.83 and 0.13, respectively. CONCLUSION: The prediction rule and its scoring system established in the study are efficacious for the calibration and discrimination of thyroid nodules in Chinese population, which could be a useful tool for the pro-operative risk stratification.

Factors influencing diagnosis of colorectal cancer: a hospital-based survey in China.

OBJECTIVE: To investigate the diagnostic status of colorectal cancer (CRC) and the influence of early diagnosis and cancer stage in a tertiary care hospital in China. METHODS: Face-to-face interviews were conducted in 364 consecutive CRC patients who had never participated in CRC screening. Initial symptoms, diagnosis and treatment delay were determined using a questionnaire. Factors influencing diagnostic status were analyzed using univariate analysis and logistic regression model. RESULTS: A total of 307 patients were enrolled, in which 128 were with colon cancer and 179 with rectal cancer. The duration of diagnosis delay was significant longer than that of treatment delay. Unlike rectal cancer, colon cancer was likely to be treated at an advanced stage with a short interval between symptom onset and treatment. Colon cancer patients with a history of biliary tract or gallbladder stones, aged ≥ 50 years and with abdominal mass or intestinal obstruction as the initial symptom were diagnosed and treated much earlier. In rectal cancer, women and non-smokers were diagnosed and treated quickly. Factors correlated with early cancer stage were found in colon cancer, including bloody stool as the initial symptom (OR = 2.63, 95% CI 1.08-6.25, P = 0.034) and a history of appendectomy (OR = 4.00, 95% CI 1.15-14.29, P = 0.029). CONCLUSIONS: The factors contributing to early cancer detection were identified but their clinical value is limited. Diagnosis by symptoms suggesting CRC needs to be improved and CRC screening should be vigorously promoted.

Derivation and validation of a prediction rule for estimating advanced colorectal neoplasm risk in average-risk Chinese.

No prediction rule is currently available for advanced colorectal neoplasms, defined as invasive cancer, an adenoma of 10 mm or more, a villous adenoma, or an adenoma with high-grade dysplasia, in average-risk Chinese. In this study between 2006 and 2008, a total of 7,541 average-risk Chinese persons aged 40 years or older who had complete colonoscopy were included. The derivation and validation cohorts consisted of 5,229 and 2,312 persons, respectively. A prediction rule was developed from a logistic regression model and then internally and externally validated. The prediction rule comprised 8 variables (age, sex, smoking, diabetes mellitus, green vegetables, pickled food, fried food, and white meat), with scores ranging from 0 to 14. Among the participants with low-risk (≤3) or high-risk (>3) scores in the validation cohort, the risks of advanced neoplasms were 2.6% and 10.0% (P < 0.001), respectively. If colonoscopy was used only for persons with high risk, 80.3% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 49.2%. The prediction rule had good discrimination (area under the receiver operating characteristic curve = 0.74, 95% confidence interval: 0.70, 0.78) and calibration (P = 0.77) and, thus, provides accurate risk stratification for advanced neoplasms in average-risk Chinese.

Body mass index increases risk for colorectal adenomas based on meta-analysis.

BACKGROUND & AIMS: There have been inconsistent results published about the relationship between excess body weight, expressed as increased body mass index (BMI), and risk of colorectal adenoma (CRA). We conducted a meta-analysis to explore this relationship. We focused on whether the relationship varied based on the sex of the study subjects, study design, features of the polyps, or potential confounders, including alcohol use, nonsteroidal anti-inflammatory drug use, smoking, and exercise. METHODS: We identified studies by performing a literature search of Medline, EMBASE, and ISI Web of Science through July 31, 2011, and by searching the reference lists of pertinent articles. We analyzed 36 independent studies, which included 29,860 incident cases of CRA. Summary relative risks with their 95% confidence intervals (CIs) were calculated with a random-effects model. Between-study heterogeneity was assessed using Cochran's Q statistic and I(2) analyses. RESULTS: Overall, a 5-unit increase in BMI (calculated as kg/m(2)) increased the risk for CRA (summary relative risk = 1.19; 95% CI: 1.13-1.26), although there was a high level of heterogeneity among studies (P(heterogeneity) < .001; I(2) = 76.8%). Subgroup analyses revealed that the increased risk of CRA in obese individuals was independent of race, geographic location, study design, sex, adenoma progression, and confounders. The association between increased BMI and risk for CRA was stronger for colon than rectal adenoma. CONCLUSIONS: Based on a meta-analysis, increased BMI increases the risk for colon but not rectal adenoma. Unlike colorectal cancer, there is no sex difference in the relationship between increased BMI and risk of CRA.

Adiponectin levels in patients with colorectal cancer and adenoma: a meta-analysis.

Inconsistent results with regard to adiponectin levels in patients with colorectal cancer (CRC) and adenoma have been reported. To evaluate adiponectin levels in patients with CRC and adenoma, a meta-analysis on studies which compared adiponectin levels in patients with CRC or adenoma with healthy controls was carried out. A literature search was performed through Pubmed, EMBASE, and Science Citation Index Expanded database. Pooled-weighted mean differences and 95% confidence intervals (95%CI) were calculated by using random-effects models. Heterogeneity between studies was assessed using the Cochran's Q and I statistics. A total of 13 studies were identified, which included 2632 cases of CRC or adenoma and 2753 healthy controls. Adiponectin levels were significantly lower in patients with CRC or adenoma compared with healthy controls, with significant heterogeneity [weighted mean differences of -1.51 (95% CI: -2.42 to -0.59; Pheterogeneity<0.001) for CRC and -1.29 (95% CI: -2.01to -0.58; Pheterogeneity<0.001) for colorectal adenoma, respectively]. On stratified analysis of CRC, significant difference in adiponectin levels between patients with CRC and healthy controls was reported only in case-control studies or small sample size studies (n<100), but not in nested case-control studies or large sample size studies (n≥100). In addition, metaregression analysis indicated that study design and sample size partly contributed to the significant heterogeneity (P=0.022 for study design and P=0.018 for sample size, respectively). For colorectal adenoma studies, stratified analysis indicated that sample size was one of the heterogeneous factors. Sensitivity analysis showed that there were no changes in the direction of effect when any one study was excluded. No publication bias was detected. Adiponectin levels are lower in patients with CRC or colorectal adenoma compared with those in healthy controls. Future studies are warranted to clarify the association of adiponectin levels and carcinogenesis of the colorectum.

High expression of delta-like ligand 4 predicts poor prognosis after curative resection for pancreatic cancer.

BACKGROUND: Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor angiogenesis, but its prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Our aim was to determine whether high DLL4 expression is correlated with poor prognosis after curative resection for PDAC. METHODS: Surgical specimens obtained from 89 patients with PDAC were immunohistochemically assessed for DLL4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression. Prognostic significance of DLL4 expression was evaluated by Kaplan-Meier method and Cox regression. The correlations of DLL4 expression with VEGFR-2 expression, tumor stage, and lymph node metastasis were examined by chi-square test and multivariate logistic regression. RESULTS: There were 38 (42.7%) and 51 patients who showed high and low DLL4 expression, respectively. Survival curves showed that patients with low DLL4 expression had a significantly better survival than those with high DLL4 expression (P < .001). Multivariate survival analysis demonstrated that high DLL4 expression was independently associated with both reduced overall survival (hazard ratio [HR] 2.24; 95% confidence interval [95% CI] 1.14-4.38) and reduced progression-free survival (HR 2.37; 95% CI 1.22-4.60). Multivariate logistic regression analyses showed that high DLL4 expression was independently associated with both advanced tumor stage (odds ratio [OR] 6.84; 95% CI 2.42-9.36) and lymph node metastasis (OR 3.27; 95% CI 1.04-10.34). We also found a positive correlation between DLL4 and VEGFR-2 expression (P < .001). CONCLUSIONS: High DLL4 expression is significantly associated with poor prognosis for surgically resected PDAC, advanced tumor stage, and lymph node metastasis. Application of adjuvant therapy targeting DLL4-Notch signaling may improve prognosis.

Colorectal cancer screening behavior and willingness: an outpatient survey in China.

AIM: To identity the factors influencing colorectal cancer (CRC) screening behavior and willingness among Chinese outpatients. METHODS: An outpatient-based face-to-face survey was conducted from August 18 to September 7, 2010 in Changhai Hospital. A total of 1200 consecutive patients aged ≥ 18 years were recruited for interview. The patient's knowledge about CRC and screening was pre-measured as a predictor variable, and other predictors included age, gender, educational level, monthly household income and health insurance status. The relationship between these predictors and screening behavior, screening willingness and screening approach were examined using Pearson's χ(2) test and logistic regression analyses. RESULTS: Of these outpatients, 22.5% had undergone CRC screening prior to this study. Patients who had participated in the screening were more likely to have good knowledge about CRC and screening (OR: 5.299, 95% CI: 3.415-8.223), have health insurance (OR: 1.996, 95% CI: 1.426-2.794) and older in age. Higher income, however, was found to be a barrier to the screening (OR: 0.633, 95% CI: 0.467-0.858). An analysis of screening willingness showed that 37.5% of the patients would voluntarily participated in a screen at the recommended age, but 41.3% would do so under doctor's advice. Screening willingness was positively correlated with the patient's knowledge status. Patients with higher knowledge levels would like to participate in the screening (OR: 4.352, 95% CI: 3.008-6.298), and they would select colonoscopy as a screening approach (OR: 3.513, 95% CI: 2.290-5.389). However, higher income level was, again, a barrier to colonoscopic screening (OR: 0.667, 95% CI: 0.505-0.908). CONCLUSION: Patient's level of knowledge and income should be taken into consideration when conducting a feasible CRC screening.

A prediction rule for estimating pancreatic cancer risk in chronic pancreatitis patients with focal pancreatic mass lesions with prior negative EUS-FNA cytology.

OBJECTIVE: Considerable false-negative endoscopic ultrasound guided fine needle aspiration (EUS-FNA) findings exist in chronic pancreatitis patients with focal pancreatic mass lesions. Our aim was to develop a prediction rule to stratify risk for pancreatic cancer in chronic pancreatitis patients with focal pancreatic mass lesions with prior negative EUS-FNA cytology. MATERIAL AND METHODS: A total of 138 eligible consecutive patients were identified from three hospitals between January 2000 and May 2008. A final diagnosis of pancreatic mass lesions was confirmed histologically or verified by a follow-up of at least 12 months. A prediction rule was developed from a logistic regression model by using a regression coefficient-based scoring method, and then internally validated by using bootstrapping. RESULTS: The rate of pancreatic cancer in the cohort was 18.1%. The prediction rule, which was scored from 0 to 10 points, comprised five variables: sex, mass location, mass number, direct bilirubin, and CA 19-9. Among the 87.7% of patients with low-risk scores (≤ 3), the risk of pancreatic cancer was 13.2%; by comparison, this risk was 52.9% (p < 0.001) among the 12.3% of patients with high-risk scores (> 3). If further invasive tests were used for patients with high risk, 36% of patients with pancreatic cancer would not be missed. The prediction rule had good discrimination (area under the receiver operating characteristic curve, 0.72) and calibration (p = 0.96). CONCLUSIONS: The prediction rule can provide available risk stratification for pancreatic cancer in chronic pancreatitis patients with focal mass lesions with prior negative EUS-FNA cytology. Application of risk stratification may improve clinical decision making.

[Factors influencing patient compliance in colorectal cancer screening: qualitative research synthesis].

OBJECTIVE: To systematically collect and analyze the influencing factors of patient compliance with colorectal cancer screening in qualitative studies so as to provide a theoretical basis for improving compliance. METHODS: The databases of Pubmed, EMbase, CBMdisc, CNKI and VIP and the relevant articles were searched. According to the predefined inclusion and exclusion criteria, the qualitative studies of the influencing factors of patient compliance with screening were included. After selection and critical appraisal of the retrieved studies, a meta-analysis was performed. RESULTS: A total of 15 studies were included. It was found that several factors had a great impact on the patient compliance of screening. They included a lack of knowledge of cancer and screening, screening costs, a feeling of embarrassment, a fear of screening complications or discomfort, barriers to implementation of screening, a lack of communication with physicians and a lack of symptoms and awareness. CONCLUSION: Screening compliance may be improved through enhancing cognitive function in patients, ameliorating physician-patient communication and lowing the screening costs.

Putative caveolin-binding sites in SARS-CoV proteins.

AIM: To obtain the information of protein-protein interaction between the SARS-CoV proteins and caveolin-1, identify the possible caveolin-binding sites in SARS-CoV proteins. METHODS: On the basis of three related caveolin-binding motifs, amino acid motif search was employed to predict the possible caveolin-1 related interaction domains in the SARS-CoV proteins. The molecular modeling and docking simulation methods were used to confirm the interaction between caveolin-1 and SARS-CoV proteins. RESULTS: Thirty six caveolin-binding motifs in the SARS-CoV proteins have been mapped out using bioinformatics analysis tools. Molecular modeling and simulation have confirmed 8 caveolin-binding sites. These caveolin-binding sites located in replicase 1AB, spike protein, orf3 protein, and M protein, respectively. CONCLUSION: Caveolin-1 may serve as a possible receptor of the SARS-CoV proteins, which may be associated with the SARS-CoV infection, replication, assembly, and budding.