Search

Background: Clinicopathological differences exist between ulcerative colitis-associated colorectal cancer (UC-CRC) and sporadic colorectal cancer (S-CRC). However, differences in the prognosis remain controversial, and the reason for these differences remains unclear. We therefore assessed the differences between patients with UC-CRC and S-CRC. Patients and Methods: This was a matched-pair analysis of the clinicopathological characteristics and prognosis of patients with UC-CRC and S-CRC who underwent colorectal resection between January 2000 and December 2021 at two institutions. Patients were matched according to age, sex, date of surgery, tumor location, and Union for International Cancer Control (UICC) stage. Results: A total of 5992 patients underwent surgery for CRC at the two institutions, and 288 patients (48 with UC-CRC and 240 with S-CRC) were matched in this study. Patients with UC-CRC underwent more invasive surgery and had a longer operative time than those with S-CRC, but there was no marked difference in postoperative complications or perioperative mortality. Long-term outcomes showed a similar 5-year overall survival (OS) for UC-CRC and S-CRC (86.5% versus 88.8%, p = 0.742); however, in stage 3 patients, patients with UC-CRC had a poorer 5-year OS than those with S-CRC (51.4% versus 83.8%, p = 0.032). The first recurrence sites in stage 3 UC-CRC were peritoneal dissemination followed by the bones, while those in S-CRC were the liver and pulmonary system. Conclusions: Despite no significant differences in surgical outcomes, patients with UC-CRC had a poorer prognosis than those with S-CRC at stage 3. The recurrence patterns in UC-CRC differed from those in S-CRC, suggesting a possible prognostic difference. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) confers an increased lifetime risk of colorectal cancer (CRC). The pathogenesis of colitis-associated CRC is considered distinct from sporadic CRC, but existing is mixed on long-term oncologic outcomes. This study aims to compare clinicopathological characteristics and survival between colitis-associated and sporadic CRC. Methods: Data was retrospectively extracted and analyzed from a single institutional database of patients with surgically resected CRC between 2004 and 2015. Patients with IBD were identified as having colitis-associated CRC. The remainder were classified as sporadic CRC. Propensity score matching was performed. Univariate and survival analyses were carried out to estimate the differences between the two groups. Results: Of 2275 patients included in this analysis, 65 carried a diagnosis of IBD (2.9%, 33 Crohn's disease, 29 ulcerative colitis, 3 indeterminate colitis). Average age at CRC diagnosis was 62 years for colitis-associated CRC and 65 for sporadic CRC. The final propensity score matched cohort consisted of 65 colitis-associated and 130 sporadic CRC cases. Patients with colitis-associated CRC were more likely to undergo total proctocolectomy (p < 0.01) and had higher incidence of locoregional recurrence (p = 0.026) compared to sporadic CRC patients. There were no significant differences in time to recurrence, tumor grade, extramural vascular invasion, perineural invasion, or rate of R0 resections. Overall survival and disease-free survival did not differ between groups. On multiple Cox regression, IBD diagnosis was not a significant predictor of survival. Conclusions: Patients with colitis-associated CRC who undergo surgical resection have comparable overall and disease-free survival to patients with sporadic CRC. [ABSTRACT FROM AUTHOR]

PurposeThe effect of vitamin D level pertinent to colorectal cancer incidence, progression, or mortality risk is complicated, and study findings are mixed. Therefore, we evaluated whether serum vitamin D [25-hydroxyvitamin D, 25(OH)D] is associated with the incidence of sporadic colorectal cancer (CRC).MethodsThis study is a retrospective analysis of the relationship between serum 25(OH)D level and the risk of CRC. Age, sex, body mass index, history of polyp, disease conditions (i.e., diabetes), medications, and other eight vitamins were used as confounding factors. A total of 389 participants were enrolled in this study, including comprising 83 CRC patients without a family history and 306 healthy controls, between January 2020 and March 2021 at the Department of Colorectal Surgery and Endoscope Center at the Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Adjusted smoothing spline plots, subgroup analysis, and multivariate logistic regression analysis were conducted to estimate the relative risk between serum 25(OH)D and sporadic CRC risk.ResultsAfter fully adjusting the confounding factors, it was found that circulating 25(OH)D played a protective role in patients with CRC (OR = 0.76 [0.63, 0.92], p = 0.004) and that an adequate vitamin D level was significantly associated with a reduced CRC risk compared to vitamin D deficiency or sufficiency (OR = 0.31 [0.11, 0.9], p = 0.03). According to this study, statins did not affect the potential protective effects of vitamin D (OR = 1.02 [0.97, 1.08], p = 0.44) and may account for the inverse association between serum 25(OH)D and colorectal cancer.ConclusionAn adequate level of serum 25(OH)D was associated with a reduced CRC risk, especially for the elderly. The finding on the absence of protective effect of vitamin D in the statin use subgroup, suggests it may be one of the substantial contributing confounders, and warrants further investigation.

Abstract Background Colitis-associated cancer (CAC) is a complication of inflammatory bowel disease (IBD) with a poor prognosis because it is often diagnosed in advanced stages with local progression or metastasis. Compared with the more common polyp-induced sporadic colorectal cancer (sCRC), CAC has different molecular mechanisms. Toll-like receptor 2 (TLR2) expression is not limited to cells related to inflammation and immune function. High levels of TLR2 expression in tumor tissues of colorectal cancer (CRC) patients have been reported. This report is to investigate the effects of knockout and knockdown of the TLR2 gene on the proliferation of CAC and sCRC. Methods Twelve C57BL/6 J wild-type mice (WT) and 12 TLR2 knockout mice (TLR2-/-) were used to rapidly establish a colitis-associated cancer (CAC) model via the 1,2-dimethylhydrazine-dextran sodium sulfate (DMH-DSS) method and were divided into the normal WT control group (NC), TLR2 knockout control group (KC), normal wild-type tumor modeling group (NT), and TLR2 knockout tumor modeling group (KT), with 6 mice in each group. The general performance of the mice during modeling, the gross changes of the colon and the rectum, and the pathological score of HE staining were used to observe tumor growth. The expression of TLR2 was detected by immunohistochemistry, and tumor proliferation was detected by Ki67 labeling. Lentivirus carrying TLR2-RNAi was used to stably infect colorectal cancer cells (HCT116 and HT29) to knock down TLR2 gene expression. The experimental groups included the uninfected control group, negative control group, and gene knockdown group. After infection, the expression of TLR2 protein was detected by Western blot, and cell proliferation and the cell cycle were detected by the CCK-8 method and fluorescence-activated cell sorting. Western blot was used to detect the expression levels of p- NF-κβ, cyclin D1 and cyclin D3 protein in each group of cells. Results TLR2 knockout in the CAC model resulted in greater changes in body weight and more severe diarrhea and colorectal hemorrhage. However, knocking out the TLR2 gene reduced the shortening of colorectal length, the number of tumors, and the total tumor volume and inhibited the growth of CAC. Knocking out the TLR2 gene also reduced the pathological score and tumor severity. TLR2 was localized in the cell membrane of the colorectal epithelium of the NC group and of the colorectal tumors of the NT group and was highly expressed in the NT group, while antigen Ki67 was localized in the nucleus of the colorectal tumor cells of the NT group and the KT group, and its expression was reduced in the KT group. In an in vitro sporadic colorectal cancer cell experiment, TLR2 protein in the TLR2 knockdown group was significantly downregulated, and TLR2 knockdown significantly inhibited the proliferation of HCT116 and HT29 colorectal cancer cells, resulting in G1 phase arrest. The expression levels of p-NF-κβ, cyclin D1 and cyclin D3 proteins in TLR2 gene knockdown group cells were significantly reduced. Conclusion Knockout and knockdown of TLR2 can inhibit the proliferation of inflammation-related colorectal cancer and sporadic colorectal cancer.

Objective: To analyze the correlation between mismatch repair-deficient (dMMR) and clinicopathological characteristics in left and right-side sporadic colorectal cancers. Methods: The clinicopathological data of 1922 patients who were pathologically confirmed as adenocarcinoma from January 2014 to September 2019 in the First Affiliated Hospital of Kunming Medical University were collected, and the dMMR and gender, age, and body mass index (BMI), ethnicity, blood type, preoperative CEA level, pathological type, tumor differentiation, tumor diameter, T stage, N stage, number of lymph nodes detected, distant metastasis, UICC stage, vascular invasion, perineural invasion were analyzed in sporadic left and right colorectal cancers. Results: A total of 1922 cases of sporadic colorectal cancer met the inclusion criteria. Patients with sporadic rightside colon cancer accounted for 23.99% (461/1922), and patients with sporadic left-side colorectal cancer accounted for 76.01% (1 461/1 922). The dMMR rate of all patients with sporadic colorectal cancer was 23.47% （451/1922), the dMMR rate of sporadic right-side colon cancer was 38.83% (179/461), and the dMMR rate of sporadic left-side colorectal cancer was 18.62% (272/1 461). Consistent with previous studies, the dMMR of all sporadic colorectal cancers in this study is more common in age < 62 years (OR = 1.551, P < 0.001), right-side colon (OR = 2.603, p < 0.001), tumor diameter≥4 cm (OR = 1.362, P = 0.009), the degree of pathological differentiation is moderate-poorly differentiated (OR = 1.538, P = 0.046), poorly differentiated (OR = 2.124, P = 0.013) and undifferentiated (OR = 1.850, P = 0.045)), UICC stages I ～II (OR = 1.340, P = 0.014), and patients without perineural invasion (OR = 1.407, P = 0.004). In sporadic right colon cancer, dMMR is more common in patients younger than 62 years old (OR = 1.888, P = 0.001), pT1～T2 (OR = 3.778, P = 0.000) and tumor diameter≥4 cm (OR = 1.856, p = 0.012); in sporadic left-side colorectal cancer, dMMR is more common in age < 62 years (OR = 1.525, P = 0.002), tumor diameter ≥4 cm (OR = 1.391, P = 0.016), and no perineural invasion (OR = 1.454，P = 0.009). Conclusions: Regardless of the primary site of intestinal tumors, dMMR is more common in patients younger than 62 years and tumor diameter≥4 cm, while no perineural invasion and pT1～T2 are more common in sporadic left-side and right-side colorectal cancers, respectively. [ABSTRACT FROM AUTHOR]

Sporadic colorectal cancer (sCRC) is the third leading cause of cancer death in the Western world. Approximately, a quarter of sCRC patients present metastatic dissemination at the moment of diagnosis, the liver being the most frequently affected organ. Additionally, this group of CRC patients is characterized by a worse prognosis. In the last decades, significant technological developments for genome analysis have fostered the identification and characterization of genetic alterations involved in the pathogenesis of sCRC. However, genetic alterations involved in the metastatic process through which tumor cells are able to colonize other tissues with a different microenvironment, still remain to be fully identified. Here, we review current knowledge about the most relevant genomic alterations involved in the liver metastatic process of sCRC, including detailed information about the genetic profile of primary colorectal tumors vs. their paired liver metastases. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) expression is commonly upregulated in sporadic colorectal cancer (CRC) and its high expression is associated with poor prognosis in patients with CRC. CA-SSR1 is a dinucleotide CA repeat of the EGFR gene that can modulate EGFR transcription and is a potential target of the mismatch repair machinery in tumours with microsatellite instability (MSI). In the present study, 160 sporadic colon cancer samples were analysed for EGFR CA-SSR1 polymorphism and MSI status. Additionally, EGFR mRNA and protein expression levels in the tumour centre and in the invasive tumour front, compared with those in adjacent normal tissue samples, were evaluated in 80 tumour samples. An inverse association was identified between EGFR mRNA levels and the sum of repeats in both alleles of the CA-SSR1 polymorphism in normal tissues. Changes in CA-SSR1 were detected in the tumour centre as well as in the invasive tumour front and metastases in all MSI high (MSI-H) tumours. Analysis of EGFR expression at the mRNA and protein levels according to MSI status revealed lower EGFR mRNA and protein expression in MSI-H tumours than microsatellite-stable (MSS) tumours. Furthermore, higher EGFR levels in the invasive tumour front compared with in the tumour centre in MSS tumours were identified, suggesting a role of EGFR in tumour progression and higher invasive potential of MSS than MSI-H tumours. [ABSTRACT FROM AUTHOR]

Abstract Background Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC. Methods We performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study. Results We identified loss of BMP5 is an early event in CRC. Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1. Conclusions Our result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.

The development of the new technologies such as the next-generation sequencing (NGS) makes more accessible the diagnosis of genetically heterogeneous diseases such as Lynch syndrome (LS). LS is one of the most common hereditary form of colorectal cancer. This autosomal dominant inherited disorder is caused by deleterious germline mutations in one of the mismatch repair (MMR) genes – MLH1, MSH2, MSH6 or PMS2, or the deletion in the EPCAM gene. These mutations eventually result in microsatellite instability (MSI), which can be easily tested in tumor tissue. According to the actual recommendations, all patients with CRC that are suspect to have LS, should be offered the MSI testing. When the MSI is positive, these patients should be recommended to genetic counseling. Here we report a pilot study about the application of NGS in the LS diagnosis in patients considered to have sporadic colorectal cancer. The inclusion criteria for the NGS testing were MSI positivity, BRAF V600E and MHL1 methylation negativity. We have used 5 gene amplicon based massive parallel sequencing on MiSeq platform. In one patient, we have identified a new pathogenic mutation in the exon 4 of the MSH6 gene that was previously not described in ClinVar, Human Gene Mutation Database, Ensembl and InSight databases. This mutation was confirmed by the Sanger method. We have shown that the implementation of new criteria for colorectal patients screening are important in clinical praxis and the NGS gene panel testing is suitable for routine laboratory settings.

Background/aim: Colorectal cancer (CRC) is a major public health problem worldwide and in Tunisia due to its increasing rate of incidence. KRAS and NRAS mutations have become a pivotal part of CRC diagnosis, given their association to treatment resistance with antiepidermal growth factor receptor (EGFR) monoclonal antibodies. In this study, we aimed to screen for mutations in KRAS and NRAS genes in Tunisian patients with CRC and explore their correlations with clinicopathological features. Materials and methods: AmoyDx KRAS and NRAS mutation real-time PCR kits were used to screen for mutations in KRAS (exon 2) and NRAS (exons 2, 3, and 4) in 96 CRC tumors. Results: KRAS exon 2 mutations were found in 41.7% (40/96) of the patients. Codon 12's most abundant mutations were G12D and G12V, followed by G12A, while G13D is the predominant mutation in codon 13. KRAS exon 2 mutations were associated with older patients (P = 0.029), left-sided tumors (P = 0.037), and greater differentiation (P = 0.044). The prevalence rate of NRAS mutations was 7.3%, mostly in exon 2. These mutations were associated with early stages of the disease (P = 0.039) and the absence of lymph node metastasis (P = 0.045). Conclusion: It can be inferred from this study that Tunisian CRC patients have a similar frequency of KRAS and NRAS mutations compared to those observed in other populations. Consequently, screening for KRAS and NRAS mutations is crucial for the orientation of therapies and the selection of appropriate candidates, while also helping to avoid unnecessary toxicity and increased costs for patients. [ABSTRACT FROM AUTHOR]

Background: Colitis-associated cancer (CAC) is a complication of inflammatory bowel disease (IBD) with a poor prognosis because it is often diagnosed in advanced stages with local progression or metastasis. Compared with the more common polyp-induced sporadic colorectal cancer (sCRC), CAC has different molecular mechanisms. Toll-like receptor 2 (TLR2) expression is not limited to cells related to inflammation and immune function. High levels of TLR2 expression in tumor tissues of colorectal cancer (CRC) patients have been reported. This report is to investigate the effects of knockout and knockdown of the TLR2 gene on the proliferation of CAC and sCRC. Methods: Twelve C57BL/6 J wild-type mice (WT) and 12 TLR2 knockout mice (TLR2-/-) were used to rapidly establish a colitis-associated cancer (CAC) model via the 1,2-dimethylhydrazine-dextran sodium sulfate (DMH-DSS) method and were divided into the normal WT control group (NC), TLR2 knockout control group (KC), normal wild-type tumor modeling group (NT), and TLR2 knockout tumor modeling group (KT), with 6 mice in each group. The general performance of the mice during modeling, the gross changes of the colon and the rectum, and the pathological score of HE staining were used to observe tumor growth. The expression of TLR2 was detected by immunohistochemistry, and tumor proliferation was detected by Ki67 labeling. Lentivirus carrying TLR2-RNAi was used to stably infect colorectal cancer cells (HCT116 and HT29) to knock down TLR2 gene expression. The experimental groups included the uninfected control group, negative control group, and gene knockdown group. After infection, the expression of TLR2 protein was detected by Western blot, and cell proliferation and the cell cycle were detected by the CCK-8 method and fluorescence-activated cell sorting. Western blot was used to detect the expression levels of p- NF-κβ, cyclin D1 and cyclin D3 protein in each group of cells. Results: TLR2 knockout in the CAC model resulted in greater changes in body weight and more severe diarrhea and colorectal hemorrhage. However, knocking out the TLR2 gene reduced the shortening of colorectal length, the number of tumors, and the total tumor volume and inhibited the growth of CAC. Knocking out the TLR2 gene also reduced the pathological score and tumor severity. TLR2 was localized in the cell membrane of the colorectal epithelium of the NC group and of the colorectal tumors of the NT group and was highly expressed in the NT group, while antigen Ki67 was localized in the nucleus of the colorectal tumor cells of the NT group and the KT group, and its expression was reduced in the KT group. In an in vitro sporadic colorectal cancer cell experiment, TLR2 protein in the TLR2 knockdown group was significantly downregulated, and TLR2 knockdown significantly inhibited the proliferation of HCT116 and HT29 colorectal cancer cells, resulting in G1 phase arrest. The expression levels of p-NF-κβ, cyclin D1 and cyclin D3 proteins in TLR2 gene knockdown group cells were significantly reduced. Conclusion: Knockout and knockdown of TLR2 can inhibit the proliferation of inflammation-related colorectal cancer and sporadic colorectal cancer. [ABSTRACT FROM AUTHOR]

Abstract Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classified into three major groups according to frequently altered/mutated genes. These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the first half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a limited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research field and discuss its prospects.

Background: Colorectal cancer (CRC) is rated as the second cause of cancer death. Genetic determinants are considered as driving forces in the development of sporadic CRC. Single-nucleotide polymorphisms (SNPs), due to their abundance in the human genome with collectively huge effect on cellular signaling pathways, are attributed as the main genetic factor in disease susceptibility including cancers. MicroRNAs are contributing to posttranslational gene regulation. They exert their regulatory function by binding to their specific recognition sequences located at 3'-untranslated region (UTR) of mRNAs. In the present study, we have elucidated the role of rs12904, a naturally occurring SNP, in the recognition site of miR200c in the 3'UTR of ephrin A1 ligand gene, in the development of sporadic CRC in the Iranian population.Materials and Methods: A case-control study using 152 CRC patients and 160 noncancerous counterparts was conducted to determine the rs12904 genotypes using polymerase chain reaction-restriction fragment length polymorphism method.Results: The results revealed no significant association between the rs12904 and sporadic CRC (odds ratio = 0.97, 95% confidence interval = 0.70-1.34). The frequency of genotypes and also alleles of the mentioned polymorphism were not significantly different between case and control groups (P = 0.765 and P = 0.847, respectively).Conclusion: The results suggest that this polymorphism probably has not a crucial role in the Iranian CRC risk and is not an important potential risk factor in molecular diagnostics of mentioned disease among the Iranian population. [ABSTRACT FROM AUTHOR]

Aim: To compare test results obtained from a PCR assay for the National Cancer Institute (NCI) five loci criteria for detecting microsatellite instability (MSI) with those obtained from immunohistochemistry of mismatch repair and a five-mononucleotide site amplification system in East Asian patients with colorectal cancer. Patients & methods: A total of 245 East Asian patients with colorectal cancer were studied retrospectively at our institution. Results: The consistency of the NCI panel PCR method compared with detection of mismatch repair protein expression by immunohistochemistry was 0.898. High level MSI (MSI-H) status was correlated with the Tumor, Node, Metastasis stage, tumor location site, metastasis, tumor grade, mucinous histological type and BRAF-type mutations. Conclusion: The NCI panel PCR assay has excellent sensitivity and specificity for detecting MSI in an East Asian population. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the expression level of DNA mismatch repair gene (MMR) in in sporadic colorectal cancer (SCRC) in eastern China, and to investigate the association between MMR status and prognosis of patients with SCRC. Patient archives from the Department of Gastrointestinal Surgery of Weihai Municipal Hospital (Weihai, China) were retrospectively collected between January 2011 and January 2012. Of the 221 consecutive patients identified, 192 patients who met the criterion were deemed eligible for inclusion. Immunohistochemistry (IHC) was conducted to detect the expression of MMR proteins MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6 and PMS1 homolog 2, mismatch repair system component (PMS2) expression and mutation in sporadic colorectal cancer (SCRC). Kaplan-Meier plots and log-rank tests were performed to conduct survival analysis and Cox proportional hazard regression models were conducted to determine independent prognostic factors. The total rate of deficient MMR (dMMR) was 14.58% (28/192): MSH6, 0.52% (1/192); PMS2, 4.17% (8/192); MSH2/MSH6, 3.65% (7/192); and MLH1/PMS2, 6.25% (12/192). The dMMR group had a significantly longer overall survival time compared with proficient MMR (pMMR) group (P=0.017). Disease-free survival time of dMMR group was also longer than pMMR group (P=0.027). Multivariate analysis using the Cox regression model confirmed that MMR status was an independent prognostic factor for SCRC. Loss of MMR expression was indicative of a favorable outcome for patients with SCRC, and MMR status could be viewed as an independent prognostic factor. [ABSTRACT FROM AUTHOR]

Background and Aim Of Study: Colorectal cancer (CRC) is among the most common cancers and accounts as the second leading cause of death from cancers in the world. RAD51 plays a crucial role in double-strand breaks repair of DNA. Single nucleotide polymorphisms within this gene could influence on the potential of DNA repair and in consequence on the susceptibility to various tumors such as CRC. This is the first report about the role of RAD51 polymorphisms in Iranian CRC susceptibility. The study was conducted to evaluate the association of 135G>C polymorphism of RAD51 gene with sporadic CRC in a subset of Iranian population.Materials and Methods: The current case-control study was performed from 2013 to 2015. One hundred patients with sporadic CRC and one hundred controls were enrolled from two referral centers in Isfahan. All samples were genotyped for the RAD51 gene using polymerase chain reaction-restriction fragment length polymorphism assay.Results: The results revealed no significant association between the RAD51 135G>C and sporadic CRC (odds ratio = 0.86, 95% confidence interval = 0.464-1.595). The frequency of genotypes and also alleles of the mentioned polymorphism were not significantly different between case and control groups (P = 0.2 and 0.4, respectively).Conclusion: The results suggest that RAD51 135G>C probably has not a crucial role in Iranian CRC risk and is not an important potential risk factor in molecular diagnostics of mentioned disease among Iranian population. [ABSTRACT FROM AUTHOR]

Purpose of Review: Colorectal cancer (CRC) is the fourth most common cancer in both men and women in the USA, resulting in over 55,000 deaths annually. Environmental and genetic factors influence the development of CRC, and inflammation is a critical hallmark of cancer that may arise from a variety of factors. While patients with inflammatory bowel disease (IBD) have a higher risk of developing CRC, sporadic CRCs may engender or be potentiated by inflammation as well. In this review, we focus on recent advances in basic and translational research utilizing murine models to understand the contribution of inflammatory signaling pathways to CRC. Recent Findings: We discuss advances in the utility of three-dimensional enteroid/colonoid/tumoroid cultures to understand immune-epithelial interactions in CRC, as well as the potential for utilizing patient-derived tumoroids for personalized therapies. Summary: This review underscores the importance of understanding the complex molecular mechanisms underlying inflammation in sporadic CRC and highlights up-and-coming or new avenues for CRC biomarkers or therapies. [ABSTRACT FROM AUTHOR]

Sporadic colorectal cancer (sCRC) is one of the most commonly diagnosed cancers worldwide, but few genetic markers have been identified and used for its early detection. MicroRNAs are diverse cellular regulators in cancer pathogenesis that bind to the 3′-untranslated region (3′-UTR) of their target mRNAs, and variants within the miRNA target sites on sCRC-related genes may influence its pathogenesis. To investigate this possibility, we used a bioinformatical method to screen SNPs for putative changes in miRNA recognition sites within the 3′-UTR of sCRC-related genes. The rs11466537 single nucleotide polymorphism was predicted to modify the regulation of hsa-miR-1193 on the Transforming Growth Factor β Receptor II (TGFBR2) gene. Additionally, luciferase reporter assays indicated that hsa-miR-1193 bound the T allele more strongly than the A allele of rs11466537 (with A being the less frequent variant), and real time-polymerase chain reaction and western blot analysis showed thatTGFBR2is significantly repressed by hsa-miR-1193. Furthermore, overexpression of hsa-miR-1193 promoted HT-29 cell proliferation, while the loss of hsa-miR-1193 inhibited the process. Finally, the rs11466537 genotyping result revealed that the frequency of A allele carriers was 1.5% in the control blood samples, but 0 in the sCRC patients' normal colon tissue samples. Our results demonstrated that hsa-miR-1193 may be involved in sCRC tumourigenesis at least in part by suppression of TGFBR2, and the A allele of rs11466537 disturbed the regulation of hsa-miR-1193 on TGFBR2. [ABSTRACT FROM PUBLISHER]

Somatic mutations of MMR gene are not often present in HNPCC and in sporadic RER+ colorectal cancers. Complete studies were made according to Bethesda and Amsterdam Criteria, and 35 patients belonged to the group with sporadic colorectal cancer, and 9 patients belonged to HNPCC group. The results of our studies showed that there is no significant difference between RER phenotype of HNPCC and sporadic cancer (p>0,05) in regard to microsatellite status. It can be a good indicator that there are so called 'susspected' on HNPCC among sporadic cancers which were not detected yet. The reason for this was an incomplete familial history of illness of patients and as such it was selected as sporadic cancer. Microsatellite analysis together with medical and familial history of illness can be a successful instrument for efficient HNPCC identification. However, successful solving of this problem lies in making an accurate diagnosis in comparative findings, which can be provided by genetic and clinical tests.

Background: Epigenetic event is a biological regulation that influences the expression of various genes involved in cancer. DNA methylation is established by DNA methyltransferases, particularly DNAmethyltransferase 3B (DNMT3B). It seems to play an oncogenic role in the creation of abnormal methylation during tumorigenesis. The polymorphisms of the DNMT3B gene may influence DNMT3B activity in DNA methylation and increase the susceptibility to several cancers. These genetic polymorphisms have been studied in several cancers in different populations. Methods: In this study, we performed a case-control study with 125 colorectal cancer patients and 135 cancer-free controls to evaluate the association between DNMT3B G39179T polymorphism (rs1569686) in the promoter region and the risk of sporadic colorectal cancer. Up to now, few studies have investigated the role of this gene variant in sporadic colorectal cancer with no familial history. The genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. Results: We found that compared with G allele carriers, statistically the DNMT3B TT genotype (%34) was significantly associated with increased risk of colorectal cancer (adjusted OR, 3.993, 95% CI, 1.726-9.238, P = 0.001). Compared with DNMT3B TT genotype, the GT and GG genotypes had lower risk of developing sporadic colorectal cancer (OR = 0.848, 95% CI = 0.436-1.650). Conclusions: Our findings were consistent with that of previously reported case-control studies with colorectal cancer. These results suggest that the DNMT3B G39179T polymorphism influences DNMT3B expression, thus contributing to the genetic susceptibility to colorectal cancer. Further mechanistic studies are needed to unravel the causal molecular mechanisms.

Colorectal cancers (CRCs) exhibiting microsatellite instability (MSI) have special biological behavior. The clinical predictors for MSI and its survival relevance for the Chinese population were still unclear. Seven hundred ninety-five CRC patients were retrospectively assessed. Mismatch repair (MMR) proteins (MSH2, MSH6, PMS1, and MLH1) expression was detected by immunohistochemistry using tumor tissues of all patients. DNA MSI status was analyzed by polymerase chain reaction in 182 samples randomly selected from the 795 cases. Among all CRC tumor tissues, 97 cases (12.2%) were with an MMR protein-deficient (MMR-D) phenotype, whereas 698 cases (87.8%) were with an MMR proteins intact (MMR-I) phenotype. A total of 21 (11.5%) CRCs were identified as having high microsatellite instability, 156 (85.7%) tumors were having microsatellite stability (MSS), and five (2.7%) were having low microsatellite instability. Importantly, MMR status was demonstrated to be moderately consistent with MSI status (k=0.845, 95% confidence interval [CI] 0.721, 0.969). Unconditional logistic regression analysis revealed age, number of lymph node, tumor diameter, and tumor site as predictors for MSI with a substantial ability to discriminate different MSI status by area under curve of 80.62% using receiver operation curve. Compared with MMR-I, MMR-D was an independent prognostic factor for longer overall survival (hazard ratio =0.340, 95% CI 0.126, 0.919; P=0.034). MMR-D is an independent prognostic factor for better outcome. Our results may provide evidence for individualized diagnosis and treatment of CRC, but this will require further validation in larger sample studies. [ABSTRACT FROM AUTHOR]

Aim Very few studies have compared the epidemiological characteristics of patients with familial colorectal cancer Type X ( FCCTX) with those of sporadic colorectal cancer (S- CRC). The aim of this study was to compare clinicopathological characteristics and survival between FCCTX and S- CRC in patients from a historically isolated geographical region. Method A retrospective study was carried out of patients with S- CRC and FCCTX treated in the Canary Islands. Family and personal history of colorectal cancer ( CRC) were recorded, together with genetic (microsatellite instability), immunohistochemical and clinical variables. Results Forty-eight (10.6%) of 451 patients were classified as FCCTX and the remaining 403 (89.4%) as S- CRC. Age at the diagnosis of tumour was significantly lower in FCCTX than in S- CRC (64.06 ± 12.65 years vs 69.13 ± 10.80 years; P = 0.01; Z = −2.48). Patients with FCCTX had a larger number of synchronous tumours ( P = 0.09). Recurrence was significantly higher in FCCTX than in S- CRC (18.7% vs 8.6%; P = 0.01). Survival correlated significantly with the number of first-degree and second-degree relatives with CRC ( P = 0.04; OR: 1.368, 95% CI: 1.01-1.84, and P = 0.04; OR: 1.363, 95% CI: 1.08-1.65) and with the total number of cases of CRC in the immediate family ( P < 0.01; OR: 1.377, 95% CI: 1.17-1.61). Recurrence-free time was significantly lower in patients with FCCTX (log-rank = 0.01). Conclusion Significant differences were found in several demographic and clinicopathological variables between patients with FCCTX and patients with S- CRC. These included increased tumour presentation under the age of 50 years and a higher recurrence rate in patients with FCCTX, suggesting an increased risk of CRC in this group. [ABSTRACT FROM AUTHOR]

Objective To investigate the impacts of perioperative blood transfusion on the immune function and prognosis in colorectal cancer (CC) patients. Methods A retrospective analysis was conducted in 1404 CC patients, including 1223 sporadic colorectal cancer (SCC) patients and 181 hereditary colorectal cancer (HCC) patients. Among them, 701 SCC and 102 HCC patients received perioperative blood transfusion. The amount of T lymphocyte subsets and natural killer (NK) cells was measured. All patients received a 10-year follow-up and relapse, metastasis and curative conditions were recorded. Results In SCC group, mortality, local recurrence and distant metastasis rate of transfused patients were significantly higher than non-transfused patients (all P  <   0.05). In HCC group, mortality was apparently higher in transfused patients than non-transfused patients ( P  = 0.002). SCC patients transfused with ≥3 U of blood had significantly higher mortality than patients transfused with <3 U ( P  = 0.006). The amount of T lymphocyte subsets and NK cells showed statistical differences before and after perioperative blood transfusion in SCC and HCC patients (all P  <   0.05). Also, there existed statistical differences in CD4+/CD8+ ratio among SCC patients before and after the perioperative blood transfusion ( P  <   0.05). CC patients who received perioperative blood transfusion had markedly lower 10-year survival rates as compared with those who did not receive (both P  <   0.05). SCC patients transfused with ≥3 U of blood had remarkably lower survival rates compared with SCC patients transfused with <3 U ( P  = 0.002). Conclusions Perioperative blood transfusion could impact immune function, increased postoperative mortality, local recurrence rate and distant metastasis rate in CC patients; and survival rate of CC patients is negatively related to blood transfusion volume. [ABSTRACT FROM AUTHOR]

Background: Experimental results indicate that riboflavin is involved in tumorigenesis. Data regarding the relationship between riboflavin and colorectal cancer (CRC) are limited, and findings vary between observational studies., Design: This was a case-control retrospective study., Objective: This study aimed to evaluate the associations between serum riboflavin level and sporadic CRC risk., Methods: In total, 389 participants were enrolled in this study - including 83 CRC patients without family history and 306 healthy controls - between January 2020 and March 2021 at the Department of Colorectal Surgery and Endoscope Center at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Age, sex, body mass index, history of polyps, disease conditions (e.g., diabetes), medications, and eight other vitamins were used as confounding factors. Adjusted smoothing spline plots, subgroup analysis, and multivariate logistic regression analysis were conducted to estimate the relative risk between serum riboflavin levels and sporadic CRC risk. After fully adjusting for the confounding factors, an increased risk of colorectal cancer was suggested for individuals with higher levels of serum riboflavin (OR = 1.08 (1.01, 1.15), p = 0.03) in a dose-response relationship., Conclusions: Our results support the hypothesis that higher levels of riboflavin may play a role in facilitating colorectal carcinogenesis. The finding of high levels of circulating riboflavin in patients with CRC warrants further investigation., Competing Interests: Conflict of interest statement The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) presents in one of three patterns: sporadic colorectal cancer in those without a family history (65-85%); those with a family history (familial CRC) 10-25% ofcases; inherited CRC accounting for less of 10% cases and presents as well-characterized cancer predisposition syndromes including Lynch syndrome (hereditary non-polyposis colorectal cancer/HNPCC) which comprises about 1-5% of all colorectal cancer, and multiple polyps CRC, which includes familial adenomatous polyposis (FAP, 1 %), rare CRC syndrome < 0.1 %). Many efforts have been made to discover the genetic and molecular features of CRC, and there is more evidence that these features determine the prognosis and response to treatment. Colorectal cancer (CRC) is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instability group, characterized by an accumulation of mutations in specific oncogens and tumor suppressor genes. The second is the microsatellite instability group, caused by the dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG island methylation phenotype (CIMP) is the third group, distinguished by hypermethylation. In this review we would like to provide an up-to-date overview of molecular genetic aspects of CRC that are currently important and should guide clinical practice in colorectal cancer in the diagnosis and selection of therapy. [ABSTRACT FROM AUTHOR]

Purpose: The effect of vitamin D level pertinent to colorectal cancer incidence, progression, or mortality risk is complicated, and study findings are mixed. Therefore, we evaluated whether serum vitamin D [25-hydroxyvitamin D, 25(OH)D] is associated with the incidence of sporadic colorectal cancer (CRC)., Methods: This study is a retrospective analysis of the relationship between serum 25(OH)D level and the risk of CRC. Age, sex, body mass index, history of polyp, disease conditions (i.e., diabetes), medications, and other eight vitamins were used as confounding factors. A total of 389 participants were enrolled in this study, including comprising 83 CRC patients without a family history and 306 healthy controls, between January 2020 and March 2021 at the Department of Colorectal Surgery and Endoscope Center at the Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Adjusted smoothing spline plots, subgroup analysis, and multivariate logistic regression analysis were conducted to estimate the relative risk between serum 25(OH)D and sporadic CRC risk., Results: After fully adjusting the confounding factors, it was found that circulating 25(OH)D played a protective role in patients with CRC (OR = 0.76 [0.63, 0.92], p = 0.004) and that an adequate vitamin D level was significantly associated with a reduced CRC risk compared to vitamin D deficiency or sufficiency (OR = 0.31 [0.11, 0.9], p = 0.03). According to this study, statins did not affect the potential protective effects of vitamin D (OR = 1.02 [0.97, 1.08], p = 0.44) and may account for the inverse association between serum 25(OH)D and colorectal cancer., Conclusion: An adequate level of serum 25(OH)D was associated with a reduced CRC risk, especially for the elderly. The finding on the absence of protective effect of vitamin D in the statin use subgroup, suggests it may be one of the substantial contributing confounders, and warrants further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Deng, Huangfu, Zhou, Wang and Shen.)

Background: The role of genetic factors in colorectal cancer pathogenesis is widely accepted. Polymorphisms are actually thought to play a role in the unexplained colorectal cancer (CRC) susceptibility. There is conflicting data regarding the role of the transforming growth factor beta receptor 1 polymorphism 6A (TGFBR1*6A) in the increased incidence of CRC. Purpose: Our aim is to test the association between this polymorphism and sporadic/familial CRC in the Lebanese population paying attention to lead time bias in the control group. This is a case-control study conducted in two Lebanese hospital centers. Materials and Methods: Cases were diagnosed with CRC during the period of 1 year prior to the study. Controls were healthy subjects aged >50 years with a history of normal colonoscopy during the period of 5 years prior to the beginning of the study. A total of 96 cases (57 sporadic/39 familial) and 97 controls were genotyped. The odds ratios for 6A carrier status was statistically significant for sporadic CRC, odds ratio (OR) = 2.314 (95 % confidence interval (CI) 1.030-5.195) but not for familial CRC. Results: No association was found between 6A carrier status and mean age at diagnosis of CRC. This is the first article in the literature to evaluate the association between 6A polymorphism and total, sporadic, and familial CRC in a single study with reduction of bias in the control group. Results are in conjunction with other studies and meta-analysis. [ABSTRACT FROM AUTHOR]

Mismatch repair (MMR) genes play an important role in the occurrence and development of sporadic colorectal cancer; however, the effect of MMR genes on clinicopathological features and prognosis remains unclear. The aim of the present study was to observe the clinical significance of MMR gene expression in sporadic colorectal cancer. Clinicopathological data and postoperative samples from 404 patients with sporadic colorectal cancer were obtained from the Affiliated Tumor Hospital of Xinjiang Medical University. The immunohistochemistry PV-9000 two-step method was performed to measure the protein expression of human mutL homolog 1 (hMLH1), human mutS homolog (hMSH) 2, human postmeiotic segregation increased 2 (hPSM2) and hMSH6. Differences in clinicopathological features, family history and survival time subsequent to surgery between groups with normal and aberrant MMR protein (MMRP) expression were compared. A total of 27.23% of all patients showed aberrant nuclear staining of MMRP. Among the patients with aberrant MMRP expression, a higher proportion of patients showed aberrant expression of more than one type of MMRP than aberrant expression of only one type of MMRP. Aberrant expression of hMLH1/hPSM2 was most commonly observed (29/404). In addition, aberrant MMRP expression in colorectal cancer was indicated predominantly in the right hemicolon. Histological type primarily showed mucinous adenocarcinoma. In addition, with increasing body mass index (BMI), the MMRP deficiency rate was also shown to increase gradually. There was a close association between MMRP expression deficiency and family history of cancer (P<0.05). For TNM stage III patients, the Kaplan-Meier survival curve showed that the aberrant MMRP expression group had a three-year disease-free survival (DFS) rate of 66.67%, which was longer than the DFS rate of the normal group (55.41%), with no statistical difference (P>0.05). In conclusion, the immunohistochemistry PV-9000 two-step method can be used to measure MMRP expression in colorectal cancer. Aberrant MMRP expression is closely correlated with tumor location, histological type, BMI and tumor family history in sporadic colorectal cancer. Aberrant MMRP expression may have an effect on the prognosis of stage III patients. [ABSTRACT FROM AUTHOR]

We evaluated the association between the presence of the GSTM1-null genotype and the combined presence of the GSTM1-null genotype/ NAT2 rapid acetylator phenotype and the risk of developing sporadic colorectal cancer (CRC), as well as their interaction with environmental risk factors. One hundred and fifty patients with sporadic CRC and 162 controls were genotyped using PCR-RFLP analysis. For testing and quantification of the simple effect (main effect) and of the gene-gene and gene-environment interaction (modification effect), univariate and multivariate logistic regression was used. In the multiplicative model, from the genetic factors, GSTM1-null and NAT2*6B had a statistically significant influence on the risk for CRC, while from the environmental factors, smoking and diet had similar effects. The combination of GSTM1-null/ NAT2 rapid acetylator phenotype/smoking behavior or GSTM1-null/ NAT2 rapid acetylator phenotype/diet rich in fried red meat was not found to influence the sporadic CRC risk in Romanians, but the GSTM1-null genotype, NAT2 rapid acetylator phenotype influenced the sporadic CRC risk differently depending on the gender of the patient. [ABSTRACT FROM AUTHOR]