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Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas and hyperplastic polyps.

ABSTRACT: OBJECTIVE:To identify modifiable factors associated with sessile serrated polyps (SSPs) and compare the association of these factors with conventional adenomas (ADs) and hyperplastic polyps (HPs). DESIGN:We 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. RESULTS:Cigarette 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. CONCLUSIONS:SSPs 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.

SUBMITTER: Davenport JR

PROVIDER: S-EPMC5432410 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas and hyperplastic polyps.

Davenport James R JR Su Timothy T Zhao Zhiguo Z Coleman Helen G HG Smalley Walter E WE Ness Reid M RM Zheng Wei W Shrubsole Martha J MJ

Gut 20161115 3

<h4>Objective</h4>To identify modifiable factors associated with sessile serrated polyps (SSPs) and compare the association of these factors with conventional adenomas (ADs) and hyperplastic polyps (HPs).<h4>Design</h4>We 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.<h4>Results</h4>Cigarette smoking was associated with increased risk for all polyps and was stronge ...[more]

PMID: 27852795

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Project description:BackgroundSessile 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.MethodsRNA-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.ResultsThe 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.ConclusionsMost 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.

Project description:Background & aimsSerrated polyps (SPs) and conventional adenomas are precursor lesions for colorectal cancer (CRC), but they are believed to arise via distinct pathways. We characterized risk factor profiles for SPs and conventional adenomas in a post hoc analysis of data from 3 large prospective studies.MethodsWe collected data from the Nurses' Health Study, the Nurses' Health Study 2, and the Health Professionals Follow-up Study on subjects who developed SPs or conventional adenomas. Our analysis comprised 141,143 participants who had undergone lower gastrointestinal endoscopy, provided updated diet and lifestyle data every 2-4 years, and were followed until diagnosis of a first polyp. We assessed 13 risk factors for CRC in patients with SPs or conventional adenomas and examined the associations according to histopathology features.ResultsWe documented 7945 SPs, 9212 conventional adenomas, and 2382 synchronous SPs and conventional adenomas during 18-20 years of follow-up. Smoking, body mass index, alcohol intake, family history of CRC, and height were associated with higher risk of SPs and conventional adenomas, whereas higher intake of vitamin D and marine omega-3 fatty acid were associated with lower risk. The associations tended to be stronger for synchronous SPs and conventional adenomas. Smoking, body mass index, and alcohol intake were more strongly associated with SPs than conventional adenomas (P for heterogeneity <.05), whereas physical activity and intake of total folate and calcium were inversely associated with conventional adenomas but not SPs. For SPs and conventional adenomas, the associations tended to be stronger for polyps in the distal colon and rectum, of 10 mm or larger or with advanced histology.ConclusionsIn an analysis of data from 3 large prospective studies, we found that although SPs and conventional adenomas share many risk factors, some factors are more strongly associated with one type of lesion than the other. These findings provide support for the etiologic heterogeneity of colorectal neoplasia.

Dataset Information

Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas and hyperplastic polyps.

Publications

Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas and hyperplastic polyps.

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