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01.05.2020 | Original Paper

Associations between molecular characteristics of colorectal serrated polyps and subsequent advanced colorectal neoplasia

verfasst von: Xinwei Hua, Polly A. Newcomb, Jessica Chubak, Rachel C. Malen, Rebecca Ziebell, Aruna Kamineni, Lee-Ching Zhu, Melissa P. Upton, Michelle A. Wurscher, Sushma S. Thomas, Hana Newman, Sheetal Hardikar, Andrea N. Burnett-Hartman

Erschienen in: Cancer Causes & Control | Ausgabe 7/2020

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Abstract

Purpose

BRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia.

Methods

Study subjects included Kaiser Permanente Washington members aged 20–75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers.

Results

We included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06–20.51).

Conclusion

Our results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors.

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Titel: Associations between molecular characteristics of colorectal serrated polyps and subsequent advanced colorectal neoplasia
verfasst von: Xinwei Hua
Polly A. Newcomb
Jessica Chubak
Rachel C. Malen
Rebecca Ziebell
Aruna Kamineni
Lee-Ching Zhu
Melissa P. Upton
Michelle A. Wurscher
Sushma S. Thomas
Hana Newman
Sheetal Hardikar
Andrea N. Burnett-Hartman
Publikationsdatum: 01.05.2020
Verlag: Springer International Publishing
Erschienen in: Cancer Causes & Control / Ausgabe 7/2020
Print ISSN: 0957-5243
Elektronische ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-020-01304-1

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Associations between molecular characteristics of colorectal serrated polyps and subsequent advanced colorectal neoplasia