Genetic test highly sensitive to colon cancer precursors

A noninvasive test to detect cancer precursors in body fluids has been shown to be able to detect genetic variations that initiate colon cancer, potentially signaling an alternative screening method to the standard colonoscopy, according to a study published Sept. 4 in Cancer Prevention Research.

The screening method described in the study is up to 5,000-fold more sensitive that other noninvasive screening methods.

“By using our technique for examining a selection of genes that become mutated during the process of colon cancer formation, it is possible to detect the very first stage of colon cancer and even precancers in a stool sample,” study author Bettina Scholtka, PhD, of the University of Potsdam in Nuthetal, Germany, said in a release. “It will be possible to prevent cancer in many cases by removing the precancerous lesions after early detection.”

Approximately 60 percent of patients with colorectal cancer have a genetic variation in the adenomatous polyposis coli (APC) gene, while 40 percent have a variation in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene. These variations are also present in precancers, and colon precancer cells carrying these genetic variations are often shed in stool samples, explained the authors.

Scholtka and colleagues used a combination of two techniques for detecting the genetic variations. Locked-nucleic acid-based, wild-type blocking (WTB) polymerase chain reaction was used to suppress normal DNA present in large quantities in a sample, while high-resolution melting (HRM) enhanced detection of genetic variations.

The authors tested the technique by first gathering a group of 80 human colon tissue samples. APC variations were detected in 41 of the 80 samples, including previously unknown variations in APC. Scholtka and colleagues then analyzed 22 stool samples from the patients with known APC variations, with the WTB-HRM technique able to detect variations in 21 out of 22 samples. Variations were also detected in the KRAS gene using a group of 20 human colon tissue samples.

The WTB-HRM method detected twice as many carcinomas and 50 percent more precursor lesions mutated in APC compared with direct sequencing, a routinely used technique for identifying variations. WTB-HRM can detect a single cancer-specific gene variation among a sample consisting of 10,000 times the amount of normal DNA, according to the authors.

“Because of its exceptionally low detection limit, the WTB-HRM method could facilitate noninvasive screening for early colorectal cancer as well as for precursor lesions by detecting cancer initiating gene mutations in body fluids like stool,” wrote the authors. They added that an interesting research question would be whether these same mutations could be detected at similar levels in plasma samples.

Scholtka said a multicenter study is needed to validate the sensitivity and specificity of the technique compared with colonoscopy.