Molecular markers of carcinogenesis for risk stratification of individuals with colorectal polyps: A case-control study

Samir Gupta, Han Sun, Sang Yi, Joy Storm, Guanghua Xiao, Bijal A. Balasubramanian, Song Zhang, Raheela Ashfaq, Don C. Rockey

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Risk stratification using number, size, and histology of colorectal adenomas is currently suboptimal for identifying patients at increased risk for future colorectal cancer.Wehypothesized that molecular markers of carcinogenesis in adenomas, measured via immunohistochemistry, may help identify high-risk patients. To test this hypothesis, we conducted a retrospective, 1:1 matched case-control study (n=216; 46% female) in which cases were patients with colorectal cancer and synchronous adenoma and controls were patients with adenoma but no colorectal cancer at baseline or within 5 years of follow-up. In phase I of analyses, we compared expression of molecular markers of carcinogenesis in case and control adenomas, blind to case status. In phase II of analyses, patients were randomly divided into independent training and validation groups to develop a model for predicting case status. We found that seven markers [p53, p21, Cox-2, b-catenin (BCAT), DNA-dependent protein kinase (DNApkcs), survivin, and O6-methylguanine-DNA methyltransferase (MGMT)] were significantly associated with case status on unadjusted analyses, as well as analyses adjusted for age and advanced adenoma status (P < 0.01 for at least one marker component). When applied to the validation set, a predictive model using these seven markers showed substantial accuracy for identifying cases [area under the receiver operation characteristic curve (AUC), 0.83; 95% confidence interval (CI), 0.74-0.92]. A parsimonious model using three markers performed similarly to the sevenmarker model (AUC, 0.84). In summary, we found that molecular markers of carcinogenesis distinguished adenomas from patients with and without colorectal cancer. Furthermore, we speculate that prospective studies using molecular markers to identify individuals with polyps at risk for future neoplasia are warranted.

Original languageEnglish (US)
Pages (from-to)1023-1034
Number of pages12
JournalCancer Prevention Research
Volume7
Issue number10
DOIs
StatePublished - Oct 1 2014

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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