Risk Factor For Development Of Colorectal Cancer Research Articles

Risk factors for colorectal cancer in a fecal immunochemical test-positive group: The National Health Insurance Service-National Health Screening Cohort.

Colorectal cancer (CRC) was the fourth most common cancer in Republic of Korea in 2019. It has a gradually increasing mortality rate, indicating the importance of screening for CRC. Among the various CRC screening test, fecal immunochemical test (FIT) is a simple yet most commonly used. Neverthelss, there have been only few long-term studies on subjects with FIT-positive. Therefore, in this study, we aimed to investigate the risk factors for CRC in FIT-positive patients using the National Health Insurance Service Bigdata database. Among 1737633 individuals with a FIT screening result for CRC in 2009, 101143 (5.82%) were confirmed to be FIT positive. The CRC incidence over 10years (up to 2018) of these participants was investigated using the National Cancer Registry. Out of the 101143 FIT-positive participants, 4395 (4.35%) were diagnosed with CRC. The FIT-positive patients who underwent a second round of screening showed a 5-year cumulative CRC incidence of approximately 1.25%, whereas those who did not showed an incidence of approximately 3.75%. Among the FIT-positive patients, the CRC incidence in the non-compliance group for the second round of screening was 2.8 times higher than that in the compliance group. In FIT-positive participants, non-compliance with the second round of screening was identified as a major risk factor for CRC development. It is necessary to establish appropriate strategies for managing risk factors for CRC in FIT-positive patients to increase the rate of compliance with the second round of CRC screening.

SelSA-1, a novel HDAC inhibitor demonstrates enhanced chemotherapeutic potential by redox modulation

Colorectal cancer (CRC) is a multistep disorder resulting from genetic and epigenetic genome changes. It is the third most common malignancy in developed nations accounting for roughly 600,000 deaths annually. Persistent gut inflammation, as observed in inflammatory bowel disease (IBD), is a key risk factor for CRC development. From an epigenetic viewpoint, the pharmacological inhibition of HDACs using HDAC inhibitors such as SAHA has emerged as a suitable anticancer strategy in the recent past. However, the clinical success of these strategies is limited and has risk factors associated with their uses. Thus, considering the critical involvement of epigenetic regulation of key molecular mechanisms in carcinogenesis as well as HDAC inhibitory and anti-tumorigenic properties of Selenium (Se), we aimed to explore the potentially safer and enhanced chemotherapeutic potential of a Se derivative of SAHA namely SelSA-1, in an experimental model of colitis-associated experimental cancer (CAC) model and mechanism involved therein. The in vitro study indicated improved efficiency, specificity, and better safety margin in terms of lower IC50 value of SelSA-1 than SAHA in both NIH3T3 (9.44 and 10.87 µM) and HCT 115 (5.70 and 7.49 µM) cell lines as well on primary colonocytes (5.61 and 6.30 µM) respectively. In an in vivo experimental model, SelSA-1 efficiently demonstrated amelioration of the multiple plaque lesions (MPLs), tumor burden/incidence, and modulation of various histological and morphological parameters. Further, redox-mediated alterations in apoptotic mediators suggested induction of cancer cell apoptosis by SelSA-1. These findings indicate the enhanced chemotherapeutic and pro-resolution effects of SelSA-1 in part mediated through redox modulation of multiple epigenetic and apoptotic pathways.

Pro-tumorigenic role of type 2 diabetes-induced cellular senescence in colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The disease still remains incurable and highly lethal in the advanced stage, representing a global health concern. Therefore, it is essential to understand the causes and risk factors leading to its development. Because age-related cellular senescence and type 2 diabetes (T2D) have been recognised as risk factors for CRC development, the recent finding that type 2 diabetic patients present an elevated circulating volume of senescent cells raises the question whether type 2 diabetes facilitates the process of CRC tumorigenesis by inducing premature cell senescence. In this review, we will discuss the mechanisms according to which T2D induces cellular senescence and the role of type 2 diabetes-induced cellular senescence in the pathogenesis and progression of colorectal cancer. Lastly, we will explore the current therapeutic approaches and challenges in targeting senescence.

Impact of AKT1 polymorphism on DNA damage, BTG2 expression, and risk of colorectal cancer development.

BackgroundAKT, also called protein kinase B, is a serine-threonine kinase that functions as a mediator of PI3K-Akt-mTOR signaling pathway and plays an important role in an array of cellular processes. Many single nucleotide polymorphisms (SNP) in AKT gene have been observed to be associated with various types of cancers. In the current research the association of a functional SNP rs1130233 in AKT, depicting G to A transition, was studied with AKT activation, DNA damage, an early response B-cell translocation gene 2 (Btg2) expression and risk of colorectal cancer (CRC) development.Patients and methodsA total 197 population-based controls and 200 CRC patients were genotyped for SNP rs1130233. AKT expression, activation and BTG2 expression were determined in GG, AG and AA genotype carriers. DNA damage was determined through comet assay.ResultsThe heterozygous AG genotype (55.67%) was more prevalent in the local population compared to homozygous wild type GG (37.78%) and homozygous AA genotypes (6.55%). Moreover, AG and AA alleles were observed to be significant contributors (P = 0.01, OR = 1.80, CI = 1.18 to 2.74, and P = 0.001, OR = 5.00, CI = 1.90 to 13.18, respectively) in increasing the risk of CRC. The immunoblot analysis revealed that G to A transition decreased the expression and activation of AKT. Moreover, AG and AA genotypes of AKT1 rs1130233 showed a significant increase in DNA damage and Btg2 expression.ConclusionsThe data concludes that G to A substitution is a risk factor for CRC development involving a decrease in AKT expression and activation and increase in DNA damage.

Interaction between microbiota and immunity and its implication in colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the world. Besides genetic causes, colonic inflammation is one of the major risk factors for CRC development, which is synergistically regulated by multiple components, including innate and adaptive immune cells, cytokine signaling, and microbiota. The complex interaction between CRC and the gut microbiome has emerged as an important area of current CRC research. Metagenomic profiling has identified a number of prominent CRC-associated bacteria that are enriched in CRC patients, linking the microbiota composition to colitis and cancer development. Some microbiota species have been reported to promote colitis and CRC development in preclinical models, while a few others are identified as immune modulators to induce potent protective immunity against colitis and CRC. Mechanistically, microbiota regulates the activation of different immune cell populations, inflammation, and CRC via crosstalk between innate and adaptive immune signaling pathways, including nuclear factor kappa B (NF-κB), type I interferon, and inflammasome. In this review, we provide an overview of the potential interactions between gut microbiota and host immunity and how their crosstalk could synergistically regulate inflammation and CRC, thus highlighting the potential roles and mechanisms of gut microbiota in the development of microbiota-based therapies to prevent or alleviate colitis and CRC.

Anthraquinone laxatives use and colorectal cancer: A systematic review and meta‐analysis of observational studies

This systematic review and meta‐analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta‐analysis using a random‐effects model. Through the meta‐analysis, we found that a history of AQ laxatives use compared with “other” and “no laxatives” use was associated with CRC development (OR: 1.41; 95% CI: 0.94–2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97–2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high‐quality studies.

Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer

Colorectal cancer (CRC) is the third most common cancer and one of the main causes of death around the world. Multiple lines of evidence have suggested the role of the...

NF-κB2 and RELB offer prognostic information in colorectal cancer and NFKB2 rs7897947 represents a genetic risk factor for disease development

The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family of transcription factors plays an important role in immune responses and cancer development and progression. We have focused on NF-κB2 and RELB of the alternative pathway of NF-κB, which remains largely underexplored in colorectal cancer (CRC). We found that NF-κB2 and RELB protein levels were upregulated in tumour and surrounding stromal tissue compared to distant non-neoplastic tissue (NN) and associated stroma (p<0.001 in all associations). Moreover, low RELB protein expression was associated with decreased overall survival (p = 0.032). Lower RELB gene expression levels were observed in tumour compared to NN tissue (p = 0.003) and were associated with shorter time to progression (TTP) (p = 0.025). NF-κB2 gene expression levels were similar in tumour and NN tissue, but higher tumour levels were prognostic for improved survival (p = 0.038) and TTP (p<0.001). We also assessed the significance of two NF-κB2 genetic polymorphisms, rs12769316 and rs7897947. Both polymorphisms were associated with lymph node infiltration (p = 0.045 and p = 0.009, respectively). In addition, rs12769316 AA homozygotes relapsed less often compared to G allele carriers (p = 0.029). Moreover, rs7897947 allele frequencies differed significantly between CRC patients and healthy controls (p<0.001) and the minor allele (G) was associated with reduced risk for developing CRC (p<0.001, OR: 0.527, 95% CI: 0.387–0.717). In conclusion, the alternative NF-κB pathway appears deregulated in CRC. Moreover, NF-κB2 and RELB expression levels seem to be significant for the clinical outcome of CRC patients and rs7897947 appears to be a risk factor for CRC development.

Effects of taurocholic acid metabolism by gut bacteria: A controlled feeding trial in adult African American subjects at elevated risk for colorectal cancer

Colorectal cancer (CRC) is the third leading cause of cancer and second leading cause of cancer death in the United States. Recent evidence has linked a high fat and animal protein diet and microbial metabolism of host bile acids as environmental risk factors for CRC development. We hypothesize that the primary bile salt taurocholic acid (TCA) is a key, diet-controlled metabolite whose use by bacteria yields a carcinogen and tumor-promoter, respectively. The work is motivated by our published data indicating hydrogen sulfide (H2S) and secondary bile acid production by colonic bacteria, serve as environmental insults contributing to CRC risk. The central aim of this study is to test whether a diet high in animal protein and saturated fat increases abundance of bacteria that generate H2S and pro-inflammatory secondary bile acids in African Americans (AAs) at high risk for CRC. Our prospective, randomized, crossover feeding trial will examine two microbial mechanisms by which an animal-based diet may support the growth of TCA metabolizing bacteria. Each subject will receive two diets in a crossover design― an animal-based diet, rich in taurine and saturated fat, and a plant-based diet, low in taurine and saturated fat. A mediation model will be used to determine the extent to which diet (independent variable) and mucosal markers of CRC risk and DNA damage (dependent variables) are explained by colonic bacteria and their functions (mediator variables). This research will generate novel information targeted to develop effective dietary interventions that may reduce the unequal CRC burden in AAs.

Hsa-miR-196a2 Rs 11614913 C&gt;T polymorphism and CRC susceptibility: A case-control study.

e16066 Background: The incidence and mortality rate of Colorectal cancer (CRC) is high worldwide. Many genetic studies have suggested that single nucleotide polymorphisms (SNPS) in genes encoding small molecule RNAs were associated with CRC risk, but the results were different in different studies. In our study, we investigated the general demographic characteristics and the relationship of hsa-mir-196a2 rs11614913 C &gt; T polymorphism and CRC susceptibility in Chinese CRC. Methods: Our study included 1,003 CRC patients and 1,303 controls. Restriction fragment length polymorphism (RFLP-PCR) method was used for genotyping and SAS version 9.4 software for statistical analysis. Results: The incidence of smoking status,alcohol use and BMI in the CRC group (25.82%,17.35%,66.80%) were much higher than that in the control subjects (20.34%,10.44%,52.80%) respectively(P &lt; 0.05). After adjusting age and other factors, hsa-mir-196a2 rs11614913 C &gt; T genotypes were not statistically correlated with CRC risk and tumor location.But the TT genotype in the hsa-mir-196a2 rs11614913 C &gt; T polymorphism reduced the risk of CRC in women (OR = 0.64, 95 CI: 0.42-0.97, P = 0.036). Conclusions: Smoking status,alcohol use and BMI may be main risk factors for CRC development in our study population.The polymorphism of hsa-mir-196a2 rs11614913 C &gt; T gene may affect the risk of CRC in women, which requires further investigation in a larger cohort in the future.

Promoter Hypermethylation of Wnt/β-catenin Signaling Pathway Inhibitor WIF-1 Gene and its Association with MTHFR C677T Polymorphism in Patients with Colorectal Cancer.

ObjectivesColorectal cancer (CRC) is a common malignancy with a high rate of mortality. The dysregulation of genes involved in the Wnt/β-catenin signaling pathway is a common finding in cancers. Wnt-inhibitory factor-1 (WIF-1) suppresses the Wnt/β-catenin signaling pathway and its inactivation by genetics and epigenetic changes may cause cancer. We investigated the DNA methylation status of the WIF-1 gene in patients with CRC and its interaction with MTHFR C677T polymorphism, a known modifier of methylation reaction.MethodsWe investigated 50 cancerous tissues and the adjacent non-cancerous tissue. Genomic DNA was extracted using a commercial kit and was treated by sodium bisulfite. Methylation-specific PCR was used for methylation analysis, and restriction fragment length polymorphism PCR to analyze the C677T polymorphism of the MTHFR gene.ResultsThe frequency of WIF1 promoter DNA methylation was significantly higher in cancerous tissue than adjacent non-cancerous tissue (52.0% vs. 8.0%; p < 0.001). WIF1 promoter DNA methylation status showed a significant association only with tumor location (p = 0.009). Carriers of TT genotype and T allele of MTHFR C677T polymorphism had a significantly higher frequency of unmethylated WIF1 gene than methylated WIF-1 gene in cancerous tissue (p = 0.025 and p = 0.001, respectively).ConclusionsPromoter DNA hypermethylation of the WIF-1 gene is a significant risk factor for CRC development, which was significantly associated with tumor location only. The significant association of TT genotype and T allele of MTHFR C677T polymorphism with unmethylated WIF-1 gene suggests a protective role for this common polymorphism against methylation-induced development of CRC.

Challenges With Colorectal Cancer Family History Assessment—Motivation to Translate Polygenic Risk Scores Into Practice

Challenges With Colorectal Cancer Family History Assessment—Motivation to Translate Polygenic Risk Scores Into Practice

Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer.

Vitamin D deficiency is repeatedly reported in colorectal cancer (CRC). Since cholesterol and vitamin D share common precursor 7-dehydrocholesterol (7-DHC), it would be important to explore the associations of key vitamin D metabolites and serum lipid parameters in patients with high and low grade CRC. The aim of this study was to analyze relationships between serum 25(OH)D3, 24,25(OH)2D3 and 7-DHC levels and serum lipids in patients with CRC, and to evaluate their potential for prediction of risk for development of high grade CRC. We recruited 82 patients CRC and 77 controls. 7-DHC, 25(OH)D3 and 24,25(OH)2D3 were quantified by LC-MS/MS methods. 7-DHC, 25(OH)D3 and vitamin D metabolic ratio (VDMR) were significantly lower in CRC patients than in control group (P<0.001, P<0.010, P<0.050 and P<0.050, respectively). 25(OH)D3 levels were higher in patients with grade I CRC when compared to grade II (P<0.050). All vitamin D metabolites positively correlated with total cholesterol (TC) concentration in CRC patients. 25(OH)D3 was significant predictor of increased CRC risk (P<0.010). After adjustment for TC concentration, 25(OH)D3 lost its predictive abilities. However, 25(OH)D3 remained significant predictor of poorly differentiated type of cancer (P<0.050). We found significant positive association between vitamin D status and serum total cholesterol. Although low 25(OH)D3 was found to be a significant risk factor for CRC development, the obtained results primarily suggest profound impact of cholesterol level on vitamin D status in CRC. However, our results suggest that low 25(OH)D3 might independently contribute to development of poorly differentiated tumor.

Insulin-Like Growth Factor 2 (IGF2) Signaling in Colorectal Cancer-From Basic Research to Potential Clinical Applications.

Colorectal cancer (CRC) is one of the most common cancers in men and women worldwide as well as is the leading cause of death in the western world. Almost a third of the patients has or will develop liver metastases. While genetic as well as epigenetic mechanisms are important in CRC pathogenesis, the basis of the most cases of cancer is unknown. High spatial and inter-patient variability of the molecular alterations qualifies this cancer in the group of highly heterogeneous tumors, which makes it harder to elucidate the mechanisms underlying CRC progression. Determination of highly sensitive and specific early diagnosis markers and understanding the cellular and molecular mechanism(s) of cancer progression are still a challenge of the current era in oncology of solid tumors. One of the accepted risk factors for CRC development is overexpression of insulin-like growth factor 2 (IGF2), a 7.5-kDa peptide produced by liver and many other tissues. IGF2 is the first gene discovered to be parentally imprinted. Loss of imprinting (LOI) or aberrant imprinting of IGF2 could lead to IGF2 overexpression, increased cell proliferation, and CRC development. IGF2 as a mitogen is associated with increased risk of developing colorectal neoplasia. Higher serum IGF2 concentration as well as its tissue overexpression in CRC compared to control are associated with metastasis. IGF2 protein was one of the three candidates for a selective marker of CRC progression and staging. Recent research indicates dysregulation of different micro- and long non-coding RNAs (miRNAs and lncRNAs, respectively) embedded within the IGF2 gene in CRC carcinogenesis, with some of them indicated as potential diagnostic and prognostic CRC biomarkers. This review systematises the knowledge on the role of genetic and epigenetic instabilities of IGF2 gene, free (active form of IGF2) and IGF-binding protein (IGFBP) bound (inactive form), paracrine/autocrine secretion of IGF2, as well as mechanisms of inducing dysplasia in vitro and tumorigenicity in vivo. We have tried to answer which molecular changes of the IGF2 gene and its regulatory mechanisms have the most significance in initiation, progression (including liver metastasis), prognosis, and potential anti-IGF2 therapy in CRC patients.

Investigating the methylation status of DACT2 gene and its association with MTHFR C677T polymorphism in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the common causes of cancer death in Iranian population. Both genetic and epigenetic changes have been implicated in CRC pathogenesis. DACT2 gene as one of the WNT signaling pathway inhibitor was shown to display tumor suppressor activity in many cancers. The aim of present study was to investigate the methylation status of DACT2 gene and its association with methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in CRC patients. Fifty formalin-fixed paraffin-embedded cancerous and adjacent healthy tissuesobtained from CRC patient were investigated. Genomic DNA was isolated using a FFPE commercial DNA extraction kit. The methylation status was evaluated by methylation specific PCR. Genotyping of MTHFR C677T polymorphism was performed using PCR-RFLP technique. Statistical analysis was done by GraphPad Prism 8. Results indicated that the frequency of methylated DACT2 gene was significantly higher in cancerous tissue relative to adjacent healthy tissue (P<0.001). DACT2 gene methylation was significantly more common among carriers of MTHFR 677CC genotype (P=0.035) and significantly less common among carriers of MTHFR 677T allele (P value =0.006). In conclusion the present study identified DACT2 gene methylation as a significant risk factor for CRC development. Moreover, the low frequency of DACT2 gene methylation among carriers of MTHFR 677T allele may confer a protective role for this common polymorphism against CRC risk.

Colonoscopy Surveillance for Advanced Adenomas Does Not Always Prevent Colorectal Cancer

Introduction: Surveillance colonoscopy is recommended after resection of advanced adenomatous polyps which are the lesions in the colon and rectum with the highest risk for malignant transformation. The frequency and risk factors associated with the development of colorectal cancer (CRC) at the polyp resection site in spite of surveillance colonoscopy may improve our ability to prevent cancer in patients with advanced adenomas. Aim: To determine the frequency and risk factors for CRC development at the resection site and other areas of the colon among individuals with high risk polyps who underwent polypectomy. Methods: Data were collected from the Mayo Clinic, Rochester, MN, electronic medical record on 14663 subjects who underwent screening and surveillance colonoscopies between 1/1990 through 12/2010 and followed up through 12/2016. We included subjects who were found to have advanced adenomatous polyps resected by colonoscopy and had at least one surveillance colonoscopy for their advanced polyps. Results: 13402 patients with advanced adenomas were included. Of the 4610/13402(34.4%) patients who had a follow-up colonoscopy within <10 years, 84/4610(1.8%) developed CRC at the polypectomy site within a median of 2.31(0.58-4.27) years. 1.2% (55/4610) developed CRC in a region of the colon distinct from the site of the advanced polyp within a median of 2.64 (1.0-6.33) years. Patients who developed CRC at the polypectomy site were most likely to have an index polyp that was villous (48.8%) and arose in the right colon (75.0%). Approximately, 25/84(30%) of patients who developed an interval CRC at the site of the advanced polyp had followed appropriate surveillance guidelines. In patients who later developed CRC at another site, their index polyp was most likely to be villous (50.0%) and to be located in the transverse colon (30.0%). 15/54(27.8%) patients had undergone recommended surveillance interval. In multivariate analysis, age (HR=1.07 [95% CI, 1.04-1.11], P<0.01); right-sided location of the index polyp (HR=5.77 [95% CI, 2.44-16.0], P<0.01), increasing polyp size(HR=1.50 [95% CI, 1.15-1.92], P<0.01); high vs low degree of dysplasia (HR =2.01[95% CI, 1.07-3.76], P =0.03); higher number of polyps resected(HR=1.12 [95% CI, 1.05-1.17], P<0.01), and piecemeal removal (HR=2.40 [95% CI, 1.13-4.97], P=0.02) were associated with an increased risk for the development of CRC at the same site as the index polyp. Polypectomy device used and mucosal lift did not correlate with an increased risk for CRC. Increasing age (HR=1.08 [95% CI, (1.04-1.12], P<0.01); right-sided location of the index AA (HR=2.73 [95% CI, 1.36-5.86], P<0.01); and sessile endoscopic appearance of the index AA (HR=3.16 [95% CI, 1.17-11.05], P =0.02) were significantly associated with an increased risk for CRC development not related to associated with index polyp. Conclusion: CRC developed in 3 %(139/4619) of patients despite careful colonoscopic surveillance. This suggests limitations in our risk stratification of polyps and our technical abilities to manage and detect polyps.FigureFigureFigureTable: Table. Colonoscopy surveillance features associated with interval CRC at the index AA/SSA polypectomy siteTable: Table. Colonoscopy surveillance features associated with interval CRC at site distinct from AA/SSA site

Race‐dependent Association of Sulfidogenic Bacteria with Colorectal Cancer

In the US, there is a higher incidence of colorectal cancer (CRC) in African Americans (AAs) compared to non‐Hispanic whites (NHWs). Recent evidence links consumption of a diet high in animal protein and fat as an environmental risk factor for CRC development, and the intestinal microbiota modulates the tumor promoting or protective effects of diet. Hydrogen sulfide, produced by resident sulfidogenic bacteria, triggers pro‐inflammatory pathways and hyper‐proliferation, and is genotoxic. We hypothesized that sulfidogenic bacterial abundance in colonic mucosa may be an environmental CRC risk factor that distinguishes AA and NHWs, and may be correlated with differences in dietary composition. Colonic biopsies from uninvolved or healthy mucosa from CRC cases and controls were collected from five medical centers through the Chicago Colorectal Cancer Consortium. Using quantitative PCR, sulfidogenic bacterial abundance was measured in uninvolved colonic mucosa of 97 AA and 56 NHW CRC cases, and 100 AA and 76 NHW controls. In addition, 16S rRNA sequencing was performed in AA cases and AA controls. A Block Brief 2000 Food Frequency Questionnaire was collected from a subset of subjects of 50 AA and 31 NHW CRC cases and 30 AA and 24 NHW controls. Differences were examined among bacterial targets, race, disease status, and dietary intake. AAs harbored a greater abundance (p&lt;0.001) of sulfidogenic bacteria compared to NHWs regardless of disease status, including the functional gene for H2S production in sulfate reducing bacteria, dissimilatory sulfate reductase (pan‐dsrA), as well as Bilophila wadsworthia‐specific dsrA, and 16S rRNA genes for Desulfobacter spp., Desulfovibrio spp., and Desulfotomaculum spp. Bilophila wadsworthia‐specific dsrA was significantly more abundant in AA cases compared to AA controls (p&lt;0.001). Linear discriminant analysis of 16S rRNA gene sequences highlighted the sulfidogenic Bilophila, Lactococcus, Odoribacter, Porphyromonas and Pyramidobacter genera as significant in AA cases. Fat intake and daily servings of meat were significantly higher (p&lt;0.01) in AAs compared with NHWs, and dietary fat intake correlated positively with pan‐dsrA abundance (p=0.011). Additionally, intake of dairy and calcium was lower (p&lt;0.001) in AA, and servings of dairy correlated negatively with pan‐dsrA abundance (p=0.007). Together, these results implicate sulfidogenic bacteria as an environmental risk factor contributing to CRC development in AAs.Support or Funding InformationThis work was supported by grants from the National Cancer Institute (U01 CA153060 and P30 CA023074, NAE; RO1 CA204808, HRG, EM, LTH; RO1 CA141057, BJ) and the American Cancer Society Illinois Division (223187, XL). PGW was supported by a predoctoral fellowship from Mayo Clinic and University of Illinois Alliance for Technology‐Based Healthcare. CY was supported by a training grant from National Institute of Health (5T32DK007788‐15). GJA was supported by a Cancer Biology Training Grant (T32CA009213).

PWE-042 Incidence and Risk Factors of Post Liver Transplant Colorectal Malignancy in PSC: Abstract PWE-042 Table 1

<h3>Introduction</h3> Patients with primary sclerosing cholangitis (PSC) and co-existing colonic inflammatory bowel disease (IBD) have an increased lifetime risk of developing colorectal cancer (CRC); a risk that persists after liver transplantation. Aim: Assess the incidence rate (I.R.) of colonic dysplasia and/or cancer in patients transplanted for PSC, and determine any factors specific to post-transplant care associated with an increased CRC risk. <h3>Methods</h3> The cohort included all patients transplanted from 1987 to 2015 for PSC with concomitant colitis. Time zero was set as the point of first liver transplant. The study end-point was the time to first dysplasia or any higher lesion. Patients were censored at time of colectomy (for a non-CRC indication), death or last date of CRC-free follow up. Statistical methods employed for determining potential risk factors included Cox-proportional hazards and Kaplan-Meier estimates. <h3>Results</h3> Overall, 306 patients were transplanted during this time period. 202 patients (66%) had underlying IBD and of this group 191 patients (95%) had co-existing colitis. The final study population was 163 patients who had colitis with an intact colon. The I.R. of developing colonic dysplasia or higher lesions was 18.9 cases per 1,000 patient years and of colonic high grade dysplasia (HGD) or neoplasia was 10.4 cases per 1,000 patient years. There has been an increase in incidence rates by year of transplant (Table 1). No risk factors for the development of colonic dysplasia or above post liver transplantation were statistically significant. These risk factors included the number of colitis flares (&gt;0, &gt;1, &gt;2), the use of cyclosporine (versus tacrolimus), the use of azathioprine (versus mycophenolate mofetil), thiopurine use, use of ursodeoxycholic acid, advancing age and male gender. <h3>Conclusion</h3> The incidence of colonic dysplasia in the PSC post-transplant population is rising. Further review of specific colitis findings need to be evaluated in order to aid in any potential risk factors for CRC development. <h3>Disclosure of Interest</h3> None Declared

The Association Between Adiposity and Survival in Patients with Colorectal Cancer

Multiple studies confirm the impact of obesity on high incidence of colorectal cancer (CRC). There is a common perception that adiposity and related metabolic dysfunctions result in worse prognosis and decreased survival among patients with a CRC diagnosis. Several epidemiologic studies confirm this observation, however the results are not always consistent, probably due to different techniques used for evaluating the degree of adiposity. Many authors suggest that the most adequate method for assessing this parameter is computer tomography of the abdomen which allows to precisely quantify the amount of adipose tissue. Excess adipose tissue is considered a metabolically active organ releasing numerous adipohormones and cytokines that stimulate chronic inflammation, insulin resistance and contribute to increased cell proliferation. However, adiposity biomarker expression are well-documented risk factors for CRC development, little is known about their prognostic value in this disease.

Never in mitosis gene A-related kinase 6 and aurora kinase A: New gene biomarkers in the conversion from ulcerative colitis to colorectal cancer.

Ulcerative colitis (UC) is an important risk factor for colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. At present, there are no studies comparing histone modification patterns of UC and CRC in the literature. Therefore the aim of the present study was to investigate whether genes, particularly those involved in histone modification, have value in patient monitoring with regards to CRC development in UC. Key gene expressions of the histone modification enzyme were assessed and compared in CRC, UC and control groups using the RT-PCR array technique. Patients were divided into subgroups based on the extent and duration of the disease and inflammatory burden, which are considered risk factors for CRC development in UC patients. In UC and CRC groups, a significantly higher overexpression of the NEK6 and AURKA genes compared to the control group was identified. In addition, there was a significantly higher overexpression of HDAC1 and PAK1 genes in the UC group, and of HDAC1, HDAC7, PAK1 and AURKB genes in the CRC group. NEK6, AURKA, HDAC1 and PAK1 were significantly overexpressed in patients with a longer UC duration. Overexpression of AURKA and NEK6 genes was significantly more pronounced in UC patients with more extensive colon involvement. HDAC1, HDAC7, PAK1, NEK6, AURKA and AURKB are important diagnostic and prognostic markers involved in the carcinogenesis of CRC. HDAC1, PAK1, NEK6 and AURKA may be considered as diagnostic markers to be used in CRC screening for UC patients.