Digestive Diseases and Sciences

, Volume 62, Issue 3, pp 678–688 | Cite as

Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue

  • Theodore R. Levin
  • Douglas A. Corley
  • Christopher D. Jensen
  • Amy R. Marks
  • Wei K. Zhao
  • Alexis M. Zebrowski
  • Virginia P. Quinn
  • Lawrence W. Browne
  • William R. Taylor
  • David A. Ahlquist
  • Graham P. Lidgard
  • Barry M. Berger
Original Article

Abstract

Background

Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in a community-based population.

Aims

To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2 years after FIT screening.

Methods

FIT-negative and FIT-positive colorectal cancer patients 50–77 years of age were matched on age, sex, and cancer stage. Adequate DNA was isolated from paraffin-embedded specimens in 210 FIT-negative and 211 FIT-positive patients. Quantitative allele-specific real-time target and signal amplification assays were performed for 7 K-ras mutations and 10 aberrantly methylated DNA biomarkers (NDRG4, BMP3, SFMBT2_895, SFMBT2_896, SFMBT2_897, CHST2_7890, PDGFD, VAV3, DTX1, CHST2_7889).

Results

One or more biomarkers were found in 414 of 421 CRCs (98.3%). Biomarker expression was not associated with FIT status, with the exception of higher SFMBT2_897 expression in FIT-negative (194 of 210; 92.4%) than in FIT-positive cancers (180 of 211; 85.3%; p = 0.02). There were no consistent differences in biomarker expression by FIT status within age, sex, stage, and cancer location subgroups.

Conclusions

The biomarkers of a currently in-use multi-target stool DNA test (K-ras, NDRG4, and BMP3) and eight newly characterized methylated biomarkers were commonly expressed in tumor tissue specimens, independent of FIT result. Additional study using stool-based testing with these new biomarkers will allow assessment of sensitivity, specificity, and clinical utility.

Keywords

Colorectal neoplasms/diagnosis DNA mutational analysis DNA neoplasm/analysis Early detection of cancer/methods 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Theodore R. Levin
    • 1
  • Douglas A. Corley
    • 2
  • Christopher D. Jensen
    • 2
  • Amy R. Marks
    • 2
  • Wei K. Zhao
    • 2
  • Alexis M. Zebrowski
    • 3
  • Virginia P. Quinn
    • 4
  • Lawrence W. Browne
    • 2
  • William R. Taylor
    • 5
  • David A. Ahlquist
    • 5
  • Graham P. Lidgard
    • 6
  • Barry M. Berger
    • 7
  1. 1.Division of Research, Kaiser Permanente Walnut Creek Medical CenterKaiser Permanente Northern CaliforniaWalnut CreekUSA
  2. 2.Division of ResearchKaiser Permanente Northern CaliforniaOaklandUSA
  3. 3.Center for Clinical Epidemiology and Biostatistics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Research and EvaluationKaiser Permanente Southern CaliforniaPasadenaUSA
  5. 5.Gastroenterology Mayo ClinicRochesterUSA
  6. 6.Research and DevelopmentExact Sciences CorporationMadisonUSA
  7. 7.Medical AffairsExact Sciences CorporationMadisonUSA

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