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Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue
Ist Teil von
Digestive diseases and sciences, 2017-03, Vol.62 (3), p.678-688
Ort / Verlag
New York: Springer US
Erscheinungsjahr
2017
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.