title: Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue.
abstract: 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.
  
  
  
  To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2 years after FIT screening.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Research, Kaiser Permanente Walnut Creek Medical Center, Kaiser Permanente Northern California, 1425 South Main Street, Walnut Creek, CA, 94596, USA.
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Levin
authors.affiliation: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Corley
authors.affiliation: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA. christopher.d.jensen@kp.org.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Jensen
authors.affiliation: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Marks
authors.affiliation: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA.
authors.forename: Wei K
authors.initials: WK
authors.lastname: Zhao
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Blockley Hall, 1st Floor, 423 Guardian Drive, Philadelphia, PA, 19104, USA.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Zebrowski
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.
authors.forename: Virginia P
authors.initials: VP
authors.lastname: Quinn
authors.affiliation: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Browne
authors.affiliation: Gastroenterology Mayo Clinic, Mayo Building, 200 First St. NW, 19th Floor, Rochester, MN, 55905, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Taylor
authors.affiliation: Gastroenterology Mayo Clinic, Mayo Building, 200 First St. NW, 19th Floor, Rochester, MN, 55905, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Ahlquist
authors.affiliation: Research and Development, Exact Sciences Corporation, 441 Charmany Dr., Madison, WI, 53719, USA.
authors.forename: Graham P
authors.initials: GP
authors.lastname: Lidgard
authors.affiliation: Medical Affairs, Exact Sciences Corporation, 441 Charmany Dr., Madison, WI, 53719, USA.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Berger
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D055398:Bone Morphogenetic Protein 3 / Q000032:analysis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D005243:Feces; D005260:Female; D020869:Gene Expression Profiling; D011905:Genes, ras / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D007120:Immunochemistry / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D008403:Mass Screening / Q000379:methods / Q000706:statistics & numerical data; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D015995:Prevalence
chemical_list: C525757:BMP3 protein, human; D014408:Biomarkers, Tumor; D055398:Bone Morphogenetic Protein 3; D005819:Genetic Markers; D009124:Muscle Proteins; C431705:NDRG4 protein, human; D009419:Nerve Tissue Proteins
keywords: Colorectal neoplasms/diagnosis; DNA mutational analysis; DNA neoplasm/analysis; Early detection of cancer/methods