Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location University of Amsterdam, Amsterdam, The Netherlands.
Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
J Pathol. 2024 Jun;263(2):217-225. doi: 10.1002/path.6276. Epub 2024 Mar 29.
Environmental factors like the pathogenicity island polyketide synthase positive (pks+) Escherichia coli (E. coli) could have potential for risk stratification in colorectal cancer (CRC) screening. The association between pks+ E. coli measured in fecal immunochemical test (FIT) samples and the detection of advanced neoplasia (AN) at colonoscopy was investigated. Biobanked FIT samples were analyzed for both presence of E. coli and pks+ E. coli and correlated with colonoscopy findings; 5020 CRC screening participants were included. Controls were participants in which no relevant lesion was detected because of FIT-negative results (cut-off ≥15 μg Hb/g feces), a negative colonoscopy, or a colonoscopy during which only a nonadvanced polyp was detected. Cases were participants with AN [CRC, advanced adenoma (AA), or advanced serrated polyp (ASP)]. Existing DNA isolation and quantitative polymerase chain reaction (qPCR) procedures were used for the detection of E. coli and pks+ E. coli in stool. A total of 4542 (90.2%) individuals were E. coli positive, and 1322 (26.2%) were pks+ E. coli positive. The prevalence of E. coli in FIT samples from individuals with AN was 92.9% compared to 89.7% in FIT samples of controls (p = 0.010). The prevalence of pks+ E. coli in FIT samples from individuals with AN (28.6%) and controls (25.9%) was not significantly different (p = 0.13). The prevalences of pks+ E. coli in FIT samples from individuals with CRC, AA, or ASP were 29.6%, 28.3%, and 32.1%, respectively. In conclusion, the prevalence of pks+ E. coli in a screening population was 26.2% and did not differ significantly between individuals with AN and controls. These findings disqualify the straightforward option of using a snapshot measurement of pks+ E. coli in FIT samples as a stratification biomarker for CRC risk. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
环境因素,如致病性岛聚酮合酶阳性(pks+)大肠杆菌(E. coli),可能对结直肠癌(CRC)筛查的风险分层具有潜在作用。本研究旨在调查粪便免疫化学检测(FIT)样本中 pks+ E. coli 的存在与结肠镜检查中晚期肿瘤(AN)检测的相关性。分析了生物样本库 FIT 样本中 E. coli 和 pks+ E. coli 的存在情况,并与结肠镜检查结果相关联;共纳入 5020 名 CRC 筛查参与者。对照组为因 FIT 结果阴性(粪便血红蛋白≥15μg/g)、阴性结肠镜检查或仅检测到非晚期息肉而未发现相关病变的参与者。病例组为 AN [CRC、高级腺瘤(AA)或高级锯齿状息肉(ASP)]患者。使用现有的 DNA 分离和定量聚合酶链反应(qPCR)程序检测粪便中的 E. coli 和 pks+ E. coli。共有 4542 名(90.2%)个体的 FIT 样本中检测到 E. coli,1322 名(26.2%)个体的 FIT 样本中检测到 pks+ E. coli。AN 患者的 FIT 样本中 E. coli 的检出率为 92.9%,而对照组为 89.7%(p=0.010)。AN 患者和对照组的 FIT 样本中 pks+ E. coli 的检出率无显著差异(p=0.13)。CRC、AA 或 ASP 患者的 FIT 样本中 pks+ E. coli 的检出率分别为 29.6%、28.3%和 32.1%。总之,筛查人群中 pks+ E. coli 的检出率为 26.2%,AN 患者与对照组之间无显著差异。这些发现否定了使用 FIT 样本中 pks+ E. coli 的单次测量作为 CRC 风险分层生物标志物的简单选项。