Using a combination of cytochrome P450 1B1 and beta-catenin for early diagnosis and prevention of colorectal cancer

Cancer Detect Prev. 2005;29(6):562-9. doi: 10.1016/j.cdp.2005.09.007. Epub 2005 Nov 10.

Abstract

Background: Although fecal occult blood test and invasive endoscopic examination are common used to detect colorectal adenomas and cancers, non-invasive and specific biomarkers are still under investigation. The objective is to evaluate the biomarker CYP1B1 alone or in combination with aryl hydrocarbon receptor (AhR), nuclear beta-catenin, p53 or bcl-2 for early diagnosis and prevention of colorectal cancer.

Methods: These biomarkers were analyzed semi-quantified across 231 colonic tissues including 97 adenocarcinomas, 85 adenomas and 49 non-neoplastic colons using immunohistochemistry. In order to differentiate non-neoplastic colons from colorectal neoplasms (adenoma and carcinoma), the values for CYP1B1, AhR, nuclear beta-catenin, p53 and bcl-2 expressions were subjected to discrimination analysis, then the cross-validation, sensitivity and specificity of these models were calculated.

Results: Expressions of CYP1B1, p53, nuclear beta-catenin and bcl-2 were significantly associated with colorectal carcinogenesis (p<0.01 for the trend test). The overexpression rates for CYP1B1, p53, nuclear beta-catenin and bcl-2 were significantly higher in the adenoma and carcinoma groups than in the non-neoplastic colon group (p<0.05). The discrimination models showed that a combination of two biomarkers was better than a single biomarker, and provided specificity ranging from 39% to 100% and sensitivity ranging from 43% to 82% for colorectal carcinoma.

Conclusions: The increase in expression of CYP1B1 occurred not only in colorectal carcinoma and but also in adenoma. Moreover, a screening panel of CYP1B1 in combination with nuclear beta-catenin was the most suitable marker pair to screen for colorectal carcinoma based on this study.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / prevention & control
  • Adenoma / diagnosis
  • Adenoma / metabolism
  • Adenoma / prevention & control
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / prevention & control*
  • Early Diagnosis
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Receptors, Aryl Hydrocarbon / biosynthesis
  • Sensitivity and Specificity
  • Steroid 11-beta-Hydroxylase / biosynthesis*
  • Tumor Suppressor Protein p53 / biosynthesis
  • beta Catenin / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Aryl Hydrocarbon
  • Tumor Suppressor Protein p53
  • beta Catenin
  • Steroid 11-beta-Hydroxylase