Can neurotensin and IL-8 levels in blood be used to identify colorectal (large bowel) cancer and adenomas (polyps)?
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer/adenomas
PROVIDER: 2411569 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:BACKGROUND & AIMS:Surveillance guidelines for serrated polyps (SPs) are based on limited data on longitudinal outcomes of patients. We used the New Hampshire Colonoscopy Registry to evaluate risk of clinically important metachronous lesions associated with SPs detected during index colonoscopies. METHODS:We collected data from a population-based colonoscopy registry that has been collecting and analyzing data on colonoscopies across the state of New Hampshire since 2004, including rates of adenoma and SP detection. Patients completed a questionnaire to determine demographic characteristics, health history, and risk factors for colorectal cancer, and were followed from index colonoscopy through all subsequent surveillance colonoscopies. Our analyses included 5433 participants (median age, 61 years; 49.7% male) with 2 colonoscopies (median time to surveillance, 4.9 years). We used multivariable logistic regression models to assess effects of index SPs (n = 1016), high-risk adenomas (HRA, n = 817), low-risk adenomas (n = 1418), and no adenomas (n = 3198) on subsequent HRA or large SPs (>1 cm) on surveillance colonoscopy (metachronous lesions). Synchronous SPs, within each index risk group, were assessed for size and by histology. SPs comprise hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas. In this study, SSA/Ps and traditional serrated adenomas are referred to collectively as STSAs. RESULTS:HRA and synchronous large SP (odds ratio [OR], 5.61; 95% confidence interval [CI], 1.72-18.28), HRA with synchronous STSA (OR, 16.04; 95% CI, 6.95-37.00), and HRA alone (OR, 3.86; 95% CI, 2.77-5.39) at index colonoscopy significantly increased the risk of metachronous HRA compared to the reference group (no index adenomas or SPs). Large index SPs alone (OR, 14.34; 95% CI, 5.03-40.86) or index STSA alone (OR, 9.70; 95% CI, 3.63-25.92) significantly increased the risk of a large metachronous SP. CONCLUSIONS:In an analysis of data from a population-based colonoscopy registry, we found index large SP or index STSA with no index HRA increased risk of metachronous large SPs but not metachronous HRA. HRA and synchronous SPs at index colonoscopy significantly increased risk of metachronous HRA. Individuals with HRA and synchronous large SP or any STSA could therefore benefit from close surveillance.
| S-EPMC5742054 | biostudies-literature
Project description:In this study we compared gene expression of precancerous SSA/Ps and benign MVHPs with particular focus on genes involved in colorectal cancer. We also identify genes whose expression can be used to differentiate SSA/Ps and MVHPs. These results provide insight into the development of SSA/Ps and illustrates differences between these related colonic polyps.
2013-07-09 | GSE43841 | GEO
Project description:ObjectiveTo identify modifiable factors associated with sessile serrated polyps (SSPs) and compare the association of these factors with conventional adenomas (ADs) and hyperplastic polyps (HPs).DesignWe used data from the Tennessee Colorectal Polyp Study, a colonoscopy-based case-control study. Included were 214 SSP cases, 1779 AD cases, 560 HP cases and 3851 polyp-free controls.ResultsCigarette smoking was associated with increased risk for all polyps and was stronger for SSPs than for ADs (OR 1.74, 95% CI 1.16 to 2.62, for current vs never, ptrend=0.008). Current regular use of non-steroidal anti-inflammatory drugs was associated with a 40% reduction in SSP risk in comparison with never users (OR 0.68, 95% CI 0.48 to 0.96, ptrend=0.03), similar to the association with AD. Red meat intake was strongly associated with SSP risk (OR 2.59, 95% CI 1.41 to 4.74 for highest vs lowest intake, ptrend<0.001) and the association with SSP was stronger than with AD (ptrend=0.003). Obesity, folate intake, fibre intake and fat intake were not associated with SSP risk after adjustment for other factors. Exercise, alcohol use and calcium intake were not associated with risk for SSPs.ConclusionsSSPs share some modifiable risk factors for ADs, some of which are more strongly associated with SSPs than ADs. Thus, preventive efforts to reduce risk for ADs may also be applicable to SSPs. Additionally, SSPs have some distinctive risk factors. Future studies should evaluate the preventive strategies for these factors. The findings from this study also contribute to an understanding of the aetiology and biology of SSPs.
| S-EPMC5432410 | biostudies-literature
Project description:See https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-to-assess-impact-of-lifestyle-advice-to-people-who-have-had-a-bowel-adenoma-removed-bewel
| 2419299 | ecrin-mdr-crc
Project description:BACKGROUND:Sessile serrated adenomas/polyps are distinguished from hyperplastic colonic polyps subjectively by their endoscopic appearance and histological morphology. However, hyperplastic and sessile serrated polyps can have overlapping morphological features resulting in sessile serrated polyps diagnosed as hyperplastic. While sessile serrated polyps can progress into colon cancer, hyperplastic polyps have virtually no risk for colon cancer. Objective measures, differentiating these types of polyps would improve cancer prevention and treatment outcome. METHODS:RNA-seq training data set and Affimetrix, Illumina testing data sets were obtained from Gene Expression Omnibus (GEO). RNA-seq single-end reads were filtered with FastX toolkit. Read mapping to the human genome, gene abundance estimation, and differential expression analysis were performed with Tophat-Cufflinks pipeline. Background correction, normalization, and probe summarization steps for Affimetrix arrays were performed using the robust multi-array method (RMA). For Illumina arrays, log2-scale expression data was obtained from GEO. Pathway analysis was implemented using Bioconductor package GSAR. To build a platform-independent molecular classifier that accurately differentiates sessile serrated and hyperplastic polyps we developed a new feature selection step. We also developed a simple procedure to classify new samples as either sessile serrated or hyperplastic with a class probability assigned to the decision, estimated using Cantelli's inequality. RESULTS:The classifier trained on RNA-seq data and tested on two independent microarray data sets resulted in zero and three errors. The classifier was further tested using quantitative real-time PCR expression levels of 45 blinded independent formalin-fixed paraffin-embedded specimens and was highly accurate. Pathway analyses have shown that sessile serrated polyps are distinguished from hyperplastic polyps and normal controls by: up-regulation of pathways implicated in proliferation, inflammation, cell-cell adhesion and down-regulation of serine threonine kinase signaling pathway; differential co-expression of pathways regulating cell division, protein trafficking and kinase activities. CONCLUSIONS:Most of the differentially expressed pathways are known as hallmarks of cancer and likely to explain why sessile serrated polyps are more prone to neoplastic transformation than hyperplastic. The new molecular classifier includes 13 genes and may facilitate objective differentiation between two polyps.
| S-EPMC5745747 | biostudies-literature
Project description:OBJECTIVES:Endoscopist quality measures such as adenoma detection rate (ADR) and serrated polyp detection rates (SPDRs) depend on pathologist classification of histology. Although variation in pathologic interpretation is recognized, we add to the literature by quantifying the impact of pathologic variability on endoscopist performance. METHODS:We used natural language processing to abstract relevant data from colonoscopy and related pathology reports performed over 2 years at four clinical sites. We quantified each pathologist's likelihood of classifying polyp specimens as adenomas or serrated polyps. We estimated the impact on endoscopists' ADR and SPDR of sending their specimens to pathologists with higher or lower classification rates. RESULTS:We observed 85,526 colonoscopies performed by 119 endoscopists; 50,453 had a polyp specimen, which were analyzed by 48 pathologists. There was greater variation across pathologists in classification of serrated polyps than in classification of adenomas. We estimate the endoscopist's average SPDR would be 0.5% if all their specimens were analyzed by the pathologist in our sample with the lowest classification rate and 12.0% if all their specimens were analyzed by the pathologist with the highest classification rate. In contrast, the endoscopist's average ADR would be 28.5% and 42.4% if their specimens were analyzed by the pathologist with lowest and highest classification rate, respectively. CONCLUSIONS:There is significant variation in pathologic interpretation, which more substantially affects endoscopist SPDR than ADR.
| S-EPMC6049074 | biostudies-literature
Project description:See https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-device-that-may-help-find-manage-polyps-bowel-during-cancer-screening-test-b-adenoma
| 2415228 | ecrin-mdr-crc
Project description:In this study we compared gene expression of precancerous SSA/Ps and benign MVHPs with particular focus on genes involved in colorectal cancer. We also identify genes whose expression can be used to differentiate SSA/Ps and MVHPs. These results provide insight into the development of SSA/Ps and illustrates differences between these related colonic polyps. Total RNA from 6 samples of normal colon, 6 microvesicular hyperplastic polyps, and 6 sessile serrated adenomas/polyps were compared
2013-07-09 | E-GEOD-43841 | biostudies-arrayexpress
Project description:Sessile serrated adenomas/polyps (SSA/Ps) are the putative precursors of the ~20% of colon cancers with the CpG island methylator phenotype (CIMP). To investigate the epigenetic phenotype of these precancers, we prospectively collected fresh-tissue samples of 17 SSA/Ps and 15 conventional adenomas (cADNs), each with a matched sample of normal mucosa. Their DNA was subjected to bisulfite next-generation sequencing to assess methylation levels at ~2.7 million CpGs located predominantly in gene regulatory regions and spanning 80.5Mb; RNA was sequenced to define the samples' transcriptomes. Compared with normal mucosa, SSA/Ps and cADNs exhibited markedly remodeled methylomes. In cADNs, hypomethylated regions were far more numerous (18,417 vs 4288 in SSA/Ps) and rarely affected CpG islands/shores. SSA/Ps seemed to have escaped this wave of demethylation. Cytosine hypermethylation in SSA/Ps was more pervasive (hypermethylated regions: 22,147 vs 15,965 in cADNs; hypermethylated genes: 4938 vs 3443 in cADNs) and more extensive (region for region), and it occurred mainly within CpG islands and shores. Given its resemblance to the CIMP typical of SSA/Ps' putative descendant colon cancers, we refer to the SSA/P methylation phenotype as proto-CIMP. Verification studies of six hypermethylated regions in an independent series of precancers demonstrated DNA methylation markers' high potential for predicting the diagnosis of SSA/Ps and cADNs. Surprisingly, proto-CIMP in SSA/Ps was associated with upregulated gene expression; downregulation was more common in cADNs. In conclusion, the epigenetic landscape of SSA/Ps differs markedly from that of cADNs. These differences are a potentially rich source of novel tissue-based and noninvasive biomarkers.
| S-EPMC6342079 | biostudies-literature
Project description:The oxysterol 27-hydroxycholesterol (27-OHC) is an endogenous selective estrogen receptor modulator implicated in breast cancer etiology. It is unknown whether circulating 27-OHC is associated with colorectal neoplasia risk. Circulating 27-OHC was measured using LC/MS in fasting plasma collected at baseline from participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial. Participants were between 45 and 75 years old, recently diagnosed with ≥1 colorectal adenoma, and followed for new colorectal polyps during colonoscopic surveillance. Adjusted risk ratios (RR) with 95% confidence intervals (CI) of new colorectal polyps were estimated for quartiles of circulating 27-OHC using log-linear regression for repeated outcomes. Polyp phenotypes included any adenomas, advanced adenomas, hyperplastic polyps, and sessile serrated adenomas/polyps. Circulating 27-OHC was measured at baseline for 1,246 participants. Compared with participants with circulating 27-OHC below the first quartile (<138 ng/mL), those with circulating 27-OHC at or above the fourth quartile (≥201 ng/mL) had 24% higher risk of adenomas (RR, 1.24; 95% CI, 1.05-1.47) and 89% higher risk of advanced adenomas (RR, 1.89; 95% CI, 1.17-3.06). Stronger associations were observed among participants with advanced adenomas at baseline. Circulating 27-OHC was not associated with risk of hyperplastic polyps (RR, 0.90; 95% CI, 0.66-1.22) or sessile serrated adenomas/polyps (RR, 1.02; 95% CI, 0.50-2.07). Circulating 27-OHC may be a risk factor for colorectal adenomas but not serrated polyps. PREVENTION RELEVANCE: This study found that plasma concentration of 27-hydroxycholesterol, a metabolite of cholesterol that regulates lipid metabolism and acts as a selective estrogen receptor modulator, is associated with the risk of developing precursor lesions for colorectal cancer.
| S-EPMC8026496 | biostudies-literature