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Objective: To determine whether risk stratification can optimize the benefits of flexible sigmoidoscopy (FSG) screening., Methods: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted from 1993 to 2001 in the United States. A colorectal cancer (CRC) risk stratification tool was developed in the control arm (n = 64,207) from the PLCO cohort and validated in the UK Biobank (n = 270,726). PLCO participants (n = 130,021) were classified into low-, medium-, and high-risk groups. Cumulative incidence and mortality were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between screening and CRC incidence and mortality., Results: The CRC risk stratification tool was based on age, gender, body mass index, smoking status, family history of CRC, diabetes, regular use of aspirin, and CRC screening history. Compared with the control arm, FSG screening was significantly associated with a reduction in mortality in both the medium-risk (HR = 0.76, 95% CI = 0.63-0.92) and high-risk groups (0.58, 0.46-0.73), but not in the low-risk group (0.85, 0.61-1.19). FSG screening also reduced distal CRC incidence and mortality in the medium-risk and high-risk groups. Furthermore, it was associated with a reduction in incidence (0.74, 0.59-0.92) and mortality (0.59, 0.40-0.87) of proximal colon cancer in the high-risk group., Conclusions: FSG screening yielded more benefits for the high-risk group than for the low-risk and medium-risk groups, supporting the development of a risk-stratified CRC screening strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Although oxaliplatin (OXA) is widely used in the frontline treatment of colorectal cancer (CRC), CRC recurrence is commonly observed due to OXA resistance. OXA resistance is associated with a number of factors, including abnormal regulation of pyroptosis. It is therefore important to elucidate the abnormal regulatory mechanism underlying pyroptosis. Here, we identified that the circular RNA circPDIA3 played an important role in chemoresistance in CRC. CircPDIA3 could induce chemoresistance in CRC by inhibiting pyroptosis both in vitro and in vivo. Mechanistically, RIP, RNA pull-down and co-IP assays revealed that circPDIA3 directly bonded to the GSDME-C domain, subsequently enhanced the autoinhibitory effect of the GSDME-C domain through blocking the GSDME-C domain palmitoylation by ZDHHC3 and ZDHHC17, thereby restraining pyroptosis. Additionally, it was found that the circPDIA3/miR-449a/XBP1 positive feedback loop increased the expression of circPDIA3 to induce chemoresistance. Furthermore, our clinical data and patient-derived tumor xenograft (PDX) models supported the positive association of circPDIA3 with development of chemoresistance in CRC patients. Taken together, our findings demonstrated that circPDIA3 could promote chemoresistance by amplifying the autoinhibitory effect of the GSDME-C domain through inhibition of the GSDME-C domain palmitoylation in CRC. This study provides novel insights into the mechanism of circRNA in regulating pyroptosis and providing a potential therapeutic target for reversing chemoresistance of CRC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Radiomics has been used in the diagnosis of tumor lymph node metastasis (LNM). However, to date, most studies have been based on intratumoral radiomics. Few studies have focused on the use of 18 F-fluorodeoxyglucose positron emission computed tomography ( 18 F-FDG PET/CT) peritumoral radiomics for the diagnosis of LNM in colorectal cancer (CRC)., Purpose: Determining the value of radiomics features extracted from 18 F-FDG PET/CT images of the peritumoral region in predicting LNM in patients with CRC., Methods: The clinical data and preoperative 18 F-FDG PET/CT images of 244 CRC patients were retrospectively analyzed. Intratumoral and peritumoral radiomics features were screened using the mutual information method, and least absolute shrinkage and selection operator regression. Based on the selected radiomics features, a radiomics score (Rad-score) was calculated, and independent risk factors obtained from univariate and multivariate logistic regression analyses were used to construct clinical and combined (Radiomics + Clinical) models. The performance of these models was evaluated using the DeLong test, while their clinical utility was assessed by decision curve analysis. Finally, a nomogram was constructed to visualize the predictive model., Results: The most optimal set of features retained by the feature filtering process were all peritumoral radiomic features. Carcinoembryonic antigen levels, PET/CT-reported lymph node status and Rad-score were found to be independent risk factors for LNM. All three LNM risk assessment models exhibited good predictive performance, with the combined model showing the best classification results, with areas under the curve of 0.85 and 0.76 in the training and validation groups, respectively. The DeLong test revealed that the performance of the combined model was superior to that of the clinical and radiomics models in both the training and validation groups, although this difference was only statistically significant in the training group. DCA indicated that the combined model displayed better clinical utility., Conclusions: 18 F-FDG PET/CT peritumoral radiomics is uniquely suited to predict the presence of LNM in patients with CRC. In particular, the predictive efficacy of LNM for precision therapy and individualized patient management can be improved by using a combination of clinical risk factors., (© 2024 American Association of Physicists in Medicine.)

Objective: Few studies have evaluated the benefits of colorectal cancer (CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model (QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and mortality., Methods: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios (HRs) and absolute risk reductions (ARRs) for CRC incidence and mortality according to risk stratification., Results: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediate- and high-risk groups [incidence: HR: 0.87, 95% confidence interval (CI): 0.81-0.94; 0.81, 0.73-0.90; mortality: 0.75, 0.64-0.87; 0.70, 0.58-0.85], which composed approximately 60% of the study population. The ARRs (95% CI) were 0.17 (0.11-0.24) and 0.43 (0.24-0.61), respectively, for CRC incidence, and 0.08 (0.05-0.11) and 0.24 (0.15-0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk groups., Conclusions: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2024 The Authors.)

Background: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC., Methods: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC., Results: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC., Conclusions: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

As one of the key metabolic enzymes in the glycolytic pathway, lactate dehydrogenase A (LDHA) might be linked to tumor proliferation by driving the Warburg effect. Circular RNAs (circRNAs) are widely implicated in tumor progression. Here, we report that circTATDN3, a circular RNA that interacts with LDHA, plays a critical role in proliferation and energy metabolism in CRC. We found that circTATDN3 expression was increased in CRC cells and tumor tissues and that high circTATDN3 expression was positively associated with poor postoperative prognosis in CRC patients. Additionally, circTATDN3 promoted the proliferation of CRC cells in vivo and vitro. Mechanistically, circTATDN3 was shown to function as an adaptor molecule that enhances the binding of LDHA to FGFR1, leading to increased LDHA phosphorylation and consequently promoting the Warburg effect. Moreover, circTATDN3 increased the expression of LDHA by sponging miR-511-5p, which synergistically promoted CRC progression and the Warburg effect. In conclusion, circTATDN3 may be a target for the treatment of CRC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To investigate the association between Kirsten rat sarcoma viral oncogene homolog (KRAS) / neuroblastoma rat sarcoma viral oncogene homolog (NRAS) /v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations and the tumor habitat-derived radiomic features obtained during pretreatment 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with colorectal cancer (CRC)., Methods: We retrospectively enrolled 62 patients with CRC who had undergone 18 F-FDG PET/computed tomography from January 2017 to July 2022 before the initiation of therapy. The patients were randomly split into training and validation cohorts with a ratio of 6:4. The whole tumor region radiomic features, habitat-derived radiomic features, and metabolic parameters were extracted from 18 F-FDG PET images. After reducing the feature dimension and selecting meaningful features, we constructed a hierarchical model of KRAS/NRAS/BRAF mutations by using the support vector machine. The convergence of the model was evaluated by using learning curve, and its performance was assessed based on the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis. The SHapley Additive exPlanation was used to interpret the contributions of various features to predictions of the model., Results: The model constructed by using habitat-derived radiomic features had adequate predictive power with respect to KRAS/NRAS/BRAF mutations, with an AUC of 0.759 (95% CI: 0.585-0.909) on the training cohort and that of 0.701 (95% CI: 0.468-0.916) on the validation cohort. The model exhibited good convergence, suitable calibration, and clinical application value. The results of the SHapley Additive explanation showed that the peritumoral habitat and a high&#95;metabolism habitat had the greatest impact on predictions of the model. No meaningful whole tumor region radiomic features or metabolic parameters were retained during feature selection., Conclusion: The habitat-derived radiomic features were found to be helpful in stratifying the status of KRAS/NRAS/BRAF in CRC patients. The approach proposed here has significant implications for adjuvant treatment decisions in patients with CRC, and needs to be further validated on a larger prospective cohort., (© 2024. The Author(s).)

Sprouty4 (SPRY4) has been frequently reported as a tumor suppressor and is therefore downregulated in various cancers. For the first time, we report that SPRY4 is epigenetically upregulated in colorectal cancer (CRC). In this study, we explored DNA methylation and hydroxymethylation levels of SPRY4 in CRC cells and patient samples and correlated these findings with mRNA and protein expression levels. Three loci within the promoter region of SPRY4 were evaluated for 5mC levels in CRC using the combined bisulfite restriction analysis. In addition, hydroxymethylation levels within SPRY4 were measured in CRC patients. Lastly, DNA methylation and mRNA expression data were extracted from CRC patients in multiple high-throughput data repositories like Gene Expression Omnibus and The Cancer Genome Atlas. Combined in vitro and in silico analysis of promoter methylation levels of SPRY4 clearly demonstrates that the distal promoter region undergoes hypomethylation in CRC patients and is associated with increased expression. Moreover, a decrease in gene body hydroxymethylation and an increase in gene body methylation within the coding region of SPRY4 were found in CRC patients and correlated with increased expression. SPRY4 is epigenetically upregulated in CRC by promoter hypomethylation and hypermethylation within the gene body that warrants future investigation of atypical roles of this established tumor suppressor.

Serrated polyps (SP) are precursors for colorectal cancer and contribute disproportionately to postcolonoscopy cancers. Leveraging three U.S. cohorts (43,974 women and 5,322 men), we developed prediction models for high-risk SPs (sized ≥10 mm or ≥3) among individuals undergoing their first colonoscopy screening. We then validated the model in the Partners Colonoscopy Cohort (51,203 women and 39,077 men). We evaluated discrimination and calibration using the C-statistic and Hosmer-Lemeshow test, respectively. The age and family history model generated a C-statistic [95% confidence interval (CI)] of 0.57 (0.56-0.58) in women and 0.58 (0.55-0.61) in men. Further inclusion of smoking, alcohol, and body mass index (the simple model) increased the C-statistic (95% CI) to 0.68 (0.67-0.69) in women and 0.68 (0.66-0.71) in men (all P < 0.001). Adding more predictors did not provide much incremental predictivity. In the validation cohort, moderate discrimination was observed in both women (0.60, 0.58-0.61) and men (0.60, 0.59-0.62). Notably, the simple model also yielded similar C-statistics for a composite endpoint of SPs and high-risk conventional adenomas (women, 0.62, 0.62-0.63; men, 0.63, 0.61-0.64). The model was adequately calibrated in both sets of cohorts. In summary, we developed and externally validated a simple prediction model based on five major risk factors for high-risk SPs that may be useful for healthy lifestyle recommendations and tailored colorectal cancer screening., Prevention Relevance: On the basis of four prospective studies in the United States, we developed and externally validated a simple risk prediction model for high-risk SPs in the setting of colonoscopy screening. Our model showed moderate discriminatory accuracy and has potential utility for individualized risk assessment, healthy lifestyle recommendations, and tailored colorectal cancer prevention., (©2023 American Association for Cancer Research.)

Oxaliplatin is commonly used in chemotherapeutic regimens for colorectal cancer (CRC) after surgical resection. However, acquired chemoresistance seriously affects the curative effect in CRC patients, and the mechanism is still unclear. Here, a circular RNA, circATG4B is identified, which plays an important role in oxaliplatin resistance in CRC. circATG4B expression is found to be increased in exosomes secreted by oxaliplatin-resistant CRC cells. In addition, the results suggest that circATG4B induces oxaliplatin resistance by promoting autophagy. Further in vivo and in vitro studies indicate that the effect of circATG4B is attributed to its potential to encode a novel protein, circATG4B-222aa. Next, circATG4B-222aa is found to function as a decoy to competitively interact with TMED10 and prevent TMED10 from binding to ATG4B, which leads to increased autophagy followed by induction of chemoresistance. Therefore, this study reveals that exosomal circATG4B participates in the decreased chemosensitivity of CRC cells, providing a new rationale for a potential therapeutic target for oxaliplatin resistance in CRC., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Conventional wisdom is that Sprouty2 (SPRY2), a suppressor of Receptor Tyrosine Kinase (RTK) signaling, functions as a tumor suppressor and is downregulated in many solid tumors. We reported, for the first time, that increased expression of SPRY2 augments cancer phenotype and Epithelial-Mesenchymal-Transition (EMT) in colorectal cancer (CRC). In this report, we assessed epigenetic DNA modifications that regulate SPRY2 expression in CRC. A total of 4 loci within SPRY2 were evaluated for 5mC using Combined Bisulfite Restriction Analysis (COBRA). Previously sequenced 5hmC nano-hmC seal data within SPRY2 promoter and gene body were evaluated in CRC. Combined bioinformatics analyses of SPRY2 CRC transcripts by RNA-seq/microarray and 450K methyl-array data archived in The Cancer Genome Atlas (TCGA) and GEO database were performed. SPRY2 protein in CRC tumors and cells was measured by Western blotting. Increased SPRY2 mRNA was observed across several CRC datasets and increased protein expression was observed among CRC patient samples. For the first time, SPRY2 hypomethylation was identified in adenocarcinomas in the promoter and gene body. We also revealed, for the first time, increases of 5hmC deposition in the promoter region of SPRY2 in CRC. SPRY2 promoter hypomethylation and increased 5hmC may play an influential role in upregulating SPRY2 in CRC.

Objective: To evaluate the diagnostic performance of quantitative fecal immunochemical testing (FIT) and to provide reference for designing effective colorectal cancer (CRC) screening strategy in China. Methods: Based on an ongoing randomized controlled trial comparing the colorectal cancer screening strategies, this current study involved 3 407 participants aged 50-74 years who had undergone colonoscopies. All the feces samples were collected from the participants prior to receiving the colonoscopy. Fecal hemoglobin (Hb) was tested by FIT following a standardized operation process. Diagnosis-related indicators of FIT were calculated using the colonoscopy results as the gold standard. Results: Among the 3 407 participants, the mean age (SD) as 60.5 (6.3) years and 1 753 (51.5%) were males. The participants involved 28 (0.8%) CRCs, 255 (7.5%) advanced adenomas, 677 (19.9%) nonadvanced adenomas, and 2 447 (71.8%) benign or negative findings. With an overall positivity rate of 2.8% (96/3 407) at the recommended cutoff value of 20 μg Hb/g, the sensitivities of FIT for both CRC and advanced adenoma were 57.1% (95 %CI : 37.2%-75.5%) and 11.0% (95 %CI : 7.4%-15.5%), respectively, with the corresponding specificity as 98.4% (95 %CI : 97.8%-98.8%). At a decreased cut-off value of 5 μg Hb/g, the sensitivities for detecting CRC and advanced adenoma increased to 64.3% (95 %CI : 44.1%-81.4%) and 16.5% (95 %CI : 12.1%-21.6%), respectively, but the specificity reduced to 95.2% (95 %CI : 94.4%-95.9%). The areas under the ROC curve for CRC and advanced adenoma were 0.908 (95 %CI : 0.842-0.973) and 0.657 (95 %CI : 0.621-0.692), respectively. Of the diagnostic performance, there were no significant differences noticed by different sex and age groups. Conclusions: In our study, the quantitative FIT showed modest sensitivity in detecting CRC but limited sensitivity in detecting advanced adenoma. In population-based CRC screening programs, the quantitative FIT had the advantage of adjusting the positive threshold based on the targeted detection rate and available resource load of colonoscopy.

To build a simple predictive model as a guide to stratify average-risk population for colonoscopy examinations. We collected data from 92 923 males without a prior history of cancer enrolled in the Kailuan Cohort Study of China. Risk factors included in the evaluation of colorectal cancer (CRC) were collected by questionnaire-based interviews at the baseline. Logistic regression coefficients for incident CRC predictors were converted into risk scores by the absolute value of the smallest coefficient in the model and rounding up to the nearest integer. Receiver operating characteristic (ROC) analysis with the leave-one-out cross-validation method was applied to evaluate model performance. In the 10-year follow-up, 353 CRC patients were in the cohort. Age, alcohol consumption, waist circumference, occupational sitting time, and history of diabetes were selected for the scoring system, and the adjusted area under the ROC was 0.66. Population in the highest risk group (16-19 points) had a 33.12-fold (95% CI: 13.44-81.59) higher risk of CRC than those in the lowest risk group. When we defined 13 points as the cut-off, the sensitivity and specificity of the scoring system for CRC were 67.99% and 62.42%, respectively. A simple scoring system for CRC has been developed to identify men at an increased relative risk of CRC within 10 years using several well-established risk factors, which allows selection of asymptomatic candidates for priority of CRC screening and saving the health resource in cancer prevention and control., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Colorectal cancer (CRC) screening has been widely implemented in many countries. However, evidence on participation and diagnostic yield of population-based CRC screening in China is sparse., Design: The analyses were conducted in the context of the Cancer Screening Program in Urban China, which recruited 1 381 561 eligible participants aged 40-69 years from 16 provinces in China from 2012 to 2015. 182 927 participants were evaluated to be high risk for CRC by an established risk score system and were subsequently recommended for colonoscopy. Participation rates and detection of colorectal neoplasms in this programme were reported and their associated factors were explored., Results: 25 593 participants undertook colonoscopy as recommended, with participation rate of 14.0%. High level of education, history of faecal occult blood test, family history of CRC and history of colonic polyp were found to be associated with the participation in colonoscopy screening. Overall, 65 CRC (0.25%), 785 advanced adenomas (3.07%), 2091 non-advanced adenomas (8.17%) and 1107 hyperplastic polyps (4.33%) were detected. Detection rates of colorectal neoplasms increased with age and were higher for men. More advanced neoplasms were diagnosed in the distal colon/rectum (65.2%). Several factors including age, sex, family history of CRC, dietary intake of processed meat and smoking were identified to be associated with the presence of colorectal neoplasms., Conclusion: The diagnostic yield was not optimal using colonoscopy screening in high-risk populations given the relatively low participation rate. Our findings will provide important references for designing effective population-based CRC screening strategies in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To systematically review available risk prediction models evidence on construction and verification of colorectal cancer risk prediction models. Methods: "Colorectal neoplasms", "risk assessment", "colorectal cancer", "colorectal tumor", "colon cancer", "colon tumor", "rectal cancer", "rectal tumor", "anal cancer", "anal tumor", "risk prediction", "malignancy", "carcinogenesis", "model" were used as search keywords. Journal papers and grey literature were searched from Chinese electronic databases (CNKI and Wanfang) and English electronic databases (PubMed and Embase) from their inception to 30 Apr 2018. The language of literature was restricted to Chinese and English. The inclusion criteria were human-oriented researches with complete information for model construction,verification and evaluation. The exclusion criteria were informal publications such as conference abstracts, Chinese disertation papers, and non-primary research materials such as reviews,letters,and news reports. Descriptive characteristics,targeted population, study design, model construction method and prediction results were extracted. A total of 36 papers involving 27 models were included. The population characteristics of all included studies,the type of research, the method of model construction and the prediction results of the model were analyzed. Results: As for model construction,there were 13 European and American population based model studies,14 Asian population based model studies,including 7 Chinese mainland based model studies. According to the factors selected into the model, these models can be divided into traditional epidemiological models (17 models), clinical index combined models (4 models),and genetic susceptibility index combined models (6 models). As for model verification,only 9 models were cross-verified in the internal population after model construction, and the extrapolation of model prediction effect was not effectively evaluated; 17 models were verified in an external population; there was only one model verified in two external populations in terms of risk prediction effect; the area under the curve of 27 models was 0.56-0.85. Conclusion: The risk prediction model of colorectal cancer is in the development stage. The external evaluation of model prediction effect is less and the prediction ability is not good, and the existing models have limited exploration of clinical indicators.

Objective: To systematically review the quality and reporting quality of colorectal cancer screening guidelines, and to provide reference for the update of colorectal cancer screening guidelines and colorectal cancer screening in China. Methods: "Colorectal cancer", "colorectal tumor", "screening", "screening", "guide", "consensus", "Colorectal cancer", "Colorectal neoplasms", "Screening", "Early Detection of Cancer", "Guideline" and "recommendation" were used as search keywords. The literature retrieval for all the Chinese and English guidelines published before April 2018 was conducted by using PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, China Biology Medicine disc (CBMdisc), Cochrane Library, Guideline International Network, China Guidelines Clearinghouse (CGC) and the official website of the US Preventive Services Task Force (USPSTF), the American Cancer Society (ACS), International Agency for Research on Cancer (IARC), Australia Cancer Council (ACC) and Association of Coloproctology of Great Britain & Ireland (ACPGBI). The inclusion criteria were independent guidance documents for colorectal cancer screening. The language is limited to Chinese and English. The exclusion criteria were literature on interpretation, evaluation, introduction, etc., as well as the translated version of the guide and old guides. The quality and reporting norms of colorectal cancer screening guidelines were compared and evaluated using the European Guideline Research and Assessment Tool (AGREE Ⅱ) and the Practice Guideline Reporting Standard (RIGHT). Results: A total of 15 guides were included. The results of the AGREE Ⅱ quality evaluation showed that the overall quality of 15 guides was high. Among them, there were 9 guides with an overall score of 50 or more, 10 with a recommendation level of "A", and 2 with a rating of "B". There were 3 guides for "C"; each guide scores higher in scope and purpose, and clarity, and scores vary greatly in the areas of participants, rigor, applicability, and independence. The results of the RIGHT evaluation showed that 15 guides were insufficient in six areas except for background information, evidence, recommendations, reviews and quality assurance, funding and conflict of interest statements and management, and other aspects. Conclusion: The overall quality of included guidelines for colorectal cancer screening is high, but the normative nature needs to be strengthened.

Objective: To investigate the association between anthropometry and colorectal cancer risk in Chinese males. Methods: Anthropometry and incident colorectal cancer cases were collected on a biennial basis starting in May 2006 among males in Kailuan Cohort (2006-2014). In addition, electronic database of hospitals affiliated to Kailuan Community, Insurance System of Kailuan Community and Tangshan were also searched for supplementary information. Cox proportional hazards regression models and linear models were used to evaluate the association between baseline anthropometry and the risk of colorectal cancer in males. Results: A total of 106 786 males were included and 318 new colorectal cancer cases were identified in the Kailuan male cohort study, with 747 337.60 person-years follow-up by 31 December 2014. The median follow-up time was 7.90 years. Highest quartile waist circumference (≥94.0 cm) or WHtR (≥0.55) had 1.45 (95 %CI : 1.05-2.02) and 1.66 (95 %CI : 1.15-2.41) higher risk of colorectal cancer when compared with lowest waist circumference (<82.0 cm) or WHtR (<0.48) after adjusting for age, education, smoking, alcohol drinking, sitting time and dust exposure. Subgroup analyses by site indicated that males with BMI ≥26.27 kg/m(2), waist circumference ≥94.0 cm or WHtR ≥0.55 had HRs (95 %CI ) of 2.18(1.27-3.73), 2.20 (1.27-3.78) and 2.42 (1.29-4.56) for colon cancer risk, respectively. Linear models showed the HR of colon cancer and 95 %CI would be 1.59 (1.24-2.02) with every 0.1 growth in WHtR. Conclusion: Obesity may be responsible for an increased risk of colorectal cancer in male. Reasonable weight control may be one of the effective measures to prevent colorectal cancer.

The development of colorectal cancer (CRC) spans about 5-10 years, making early detection and prevention beneficial to the survival of CRC patients. To address inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta-analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were included in the meta-analysis after screening 120 articles. The following items were collected from each study: author, published year, country, patient gender, MGMT methylation status, and patients' disease progression. Pooled hazard ratios and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or random effect models depending on the heterogeneity between studies. The overall survival of CRC patients was found not to be significantly associated with MGMT methylation. Further subgroup analysis showed that the frequency of MGMT methylation was significantly higher in CRC than in normal tissues (p < 0.00001). MGMT promoter in CRC patients was more frequently methylated than in adenoma patients. In addition, MGMT methylation was significantly increased in adenoma than in normal tissues (p < 0.0001). In conclusion, MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade. However, MGMT methylation is not associated with the prognosis of CRC.

Colorectal cancer(CRC) cell lines are ideal in vitro models for colorectal cancer study. Although the number of colorectal cell lines increases hence provides diversified choices for research, several problems occur including the uneven quality control, insufficient attention to the origin and biological characteristics of CRC cell lines, resulting in inappropriate selection of CRC cell lines for study. In this paper, we classify the current CRC cell lines for study, review the biological characteristics, current problems of experiment choices, and discuss the exact choice of cell lines for CRC study.

Objective: To investigate the methylation in promtor region of RASSF2 and sFRP1 in sporadic colorectal cancer patients in order to provide screening method for early colorectal cancer., Methods: The methylation in promoter region of RASSF2 and sFRP1 in serum samples of 59 sporadic colorectal cancer patients and 59 healthy volunteers was detected by methylation specific PCR. The association between clinicopathological features of sporadic colorectal cancer patients and methylation in promoter region of RASSF2 and sFRP1 was analyzed., Results: The methylation rates of RASSF2 and sFRP1 gene in serum of 59 sporadic colorectal cancer patients were 27.1% and 30.5%, significantly higher than those in healthy volunteers(0%, both P<0.01). The methylation of RASSF2 or sFRP1 occurred in 29(49.2%) patients, which was significantly higer than the methylation rate of single gene(P<0.05). No association was found between methylation ratio of RASSF2 and sFRP1 and clinicopathological features in sporadic colorectal cancer patients., Conclusions: Methylation in promoter region of RASSF2 and sFRP1 is often detected in serum of colorectal cancer patients. The combination detection of methylation for the two genes may provide information for early screening of colorectal cancer.