Dataset Information

Colorectal Cancer Risk by Genetic Variants in Populations With and Without Colonoscopy History.

ABSTRACT:

Background

Polygenic risk scores (PRS), which are derived from results of large genome-wide association studies, are increasingly propagated for colorectal cancer (CRC) risk stratification. The majority of studies included in the large genome-wide association studies consortia were conducted in the United States and Germany, where colonoscopy with detection and removal of polyps has been widely practiced over the last decades. We aimed to assess if and to what extent the history of colonoscopy with polypectomy may alter metrics of the predictive ability of PRS for CRC risk.

Methods

A PRS based on 140 single nucleotide polymorphisms was compared between 4939 CRC patients and 3797 control persons of the Darmkrebs: Chancen der Verhütung durch Screening (DACHS) study, a population-based case-control study conducted in Germany. Risk discrimination was quantified according to the history of colonoscopy and polypectomy by areas under the curves (AUCs) and their 95% confidence intervals (CIs). All statistical tests were 2-sided.

Results

AUCs and 95% CIs were higher among subjects without previous colonoscopy (AUC = 0.622, 95% CI = 0.606 to 0.639) than among those with previous colonoscopy and polypectomy (AUC = 0.568, 95% CI = 0.536 to 0.601; difference [? AUC] = 0.054, P?=?.004). Such differences were consistently seen in sex-specific groups (women: ? AUC = 0.073, P?=?.02; men: ? AUC = 0.046, P?=?.048) and age-specific groups (younger than 70?years: ? AUC = 0.052, P?=?.07; 70?years or older: ? AUC = 0.049, P?=?.045).

Conclusions

Predictive performance of PRS may be underestimated in populations with widespread use of colonoscopy. Future studies using PRS to develop CRC prediction models should carefully consider colonoscopy history to provide more accurate estimates.

SUBMITTER: Guo F

PROVIDER: S-EPMC7898082 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Colorectal Cancer Risk by Genetic Variants in Populations With and Without Colonoscopy History.

Guo Feng F Chen Xuechen X Chang-Claude Jenny J Hoffmeister Michael M Brenner Hermann H

JNCI cancer spectrum 20210123 1

<h4>Background</h4>Polygenic risk scores (PRS), which are derived from results of large genome-wide association studies, are increasingly propagated for colorectal cancer (CRC) risk stratification. The majority of studies included in the large genome-wide association studies consortia were conducted in the United States and Germany, where colonoscopy with detection and removal of polyps has been widely practiced over the last decades. We aimed to assess if and to what extent the history of colon ...[more]

PMID: 33644683

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Project description:INTRODUCTION: Several studies evaluated the prevalence of Lynch Syndrome (LS) in young onset colorectal cancer (CRC) patients and the results were extremely variable (5%-20%). Immunohistochemistry (IHC) for MMR proteins and/or MSI analysis are screening tests that are done, either by themselves or in conjunction, on colon cancer tissue to identify individuals at risk for LS. The primary aim of our study was to evaluate the prevalence of LS in a large series of early-onset CRC without family history compared with those with family history. The secondary aim was to assess the diagnostic accuracy of IHC and MSI analysis as pre-screening tools for LS. METHODS: Early-onset CRC patients (? 50 years) were prospectively recruited in the study. IHC and MSI analysis were performed in all the patients. Germ-line mutation analysis (GMA) was carried out in all MMR deficient tumors. A logistic regression model was performed to identify clinical features predictive of MSI-H. RESULTS: 117 early onset CRC cases were categorized in three groups (A, B, C) according with family history of CRC. IHC and MSI analysis showed MMR deficiency in 6/70 patients (8.6%) of group A, 24/40 patients (60%) of group B and none of group C. GMA showed a deleterious mutation in 19 (47.5%) patients of group B. MSI analysis had a diagnostic accuracy of 95.7% (CI 92.1-99.4) and IHC of 83.8% (CI 77.1-90.4). The logistic regression model revealed that by using a combination of the two features "No Amsterdam Criteria" and "left sided CRC" to exclude MSI-H, accuracy was 89.7% (84.2-95.2). CONCLUSIONS: Early-onset CRC patients, with left sided CRC and without family history are "at very low risk" for Lynch syndrome. The two simple criteria of family history and CRC site could be used as a pre-screening tool to evaluate whether or not patients should undergo tissue molecular screening. In the few cases of suspected LS (right sided CRC and/or Amsterdam Criteria), a reasonable approach could be to perform MSI analysis first and IHC afterwards only in MSI-H patients.

Dataset Information

Colorectal Cancer Risk by Genetic Variants in Populations With and Without Colonoscopy History.

Background

Methods

Results

Conclusions

Publications

Colorectal Cancer Risk by Genetic Variants in Populations With and Without Colonoscopy History.

Similar Datasets

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