Assessment of Septin9 Biomarker for Detection of Colorectal Cancer in Patients With Positive Fecal Immunochemical Test

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States and
affects men and women almost equally. The United States Preventative Services Task Force
(USPSTF) currently recommends screening with any of three options, which include fecal
testing, flexible sigmoidoscopy, or colonoscopy.

Screening for CRC with fecal occult blood testing (using a guaiac-based test) done annually
or biennially has been shown to decrease mortality 15-33% primarily through detection of
early stage cancer. Guaiac fecal occult blood testing (gFOBT) has a known positive balance
of benefit and risk in screening populations, is the least expensive, and is the preferred
method of screening in 30-55% of patients. The fecal immunochemical test (FIT) offers
significant improvements over the gFOBT, most notably that it is easier to use (requires
fewer samples and no dietary or medication restrictions) and is more sensitive than the
gFOBT with respect to detecting both CRC and precancerous adenomas. As a result of improved
test performance and usability, in 2008 multiple professional societies endorsed the use of
four types of FITs for colorectal cancer screening. Kaiser Permanente currently uses the
OC-Micro FIT as the fecal screening test in all regions.

In recent years, intensive efforts have been undertaken to identify blood-based markers that
may provide a promising alternative or supplement to fecal testing for non-invasive CRC
screening. One method under development is to identify aberrantly methylated genes in cancer
tissue through a blood test. Prior studies have explored those specific colorectal cancer
genes that show the highest differences in methylation between the cancer and background
genetic expression. Of these, methylation of the Septin 9 gene through a qPCR assay is
relatively well studied.

The proposed study aims to evaluate whether the Septin 9 biomarker may be used to supplement
the OC-Micro FIT for colorectal cancer screening in such a way as to safely reduce unneeded
colonoscopies. The population of interest for this study—those with a positive screening
OC-Micro fecal immunochemical test—has a CRC prevalence of approximately 5%. Knowing how
well Septin 9 can identify those without cancer prior to colonoscopy is important largely
because colonoscopy, even when done diagnostically (e.g., after a positive FIT result), can
cause serious complications.