Genetic Testing Targets Risk Factor for Colon Cancer

A screening procedure has been developed that radically increases testing for Lynch syndrome, a hereditary genetic disorder that increases cancer risk.

Paraffin-embedded biopsies from cancerous tissue can be examined for certain mutations in genes that repair DNA by testing different DNA markers for irregularities.

Pathologists at the Mayo Clinic (Rochester, MN, USA) tested all resected newly diagnosed colorectal cancers in patients who were less than 51 years of age, from 2003 to 2008. All the patients automatically underwent polymerase chain reaction (PCR)-based microsatellite instability (MSI) testing if there was no testing prior to surgical resection. In MSI, DNA is isolated from normal and cancer tissue is then PCR-amplified across mononucleotide microsatellites and analyzed by fluorescent capillary electrophoresis. Allelic profiles from the normal and malignant tissue are compared to determine the MSI status which is reported as microsatellite instability high (MSI-H), an abnormal result, or microsatellite instability low or stable (MSI-L or MSS), both normal results. Patients with a history of inflammatory bowel disease or polyposis syndrome were excluded.

Over the five-year period, 210 of 258 newly diagnosed young patients undergoing surgery, 128 had preoperative and 82 postoperative testing. Of the 48 not tested, 29 eligible for postoperative reflex testing were missed, 15 had a complete pathological response after neoadjuvant therapy, and four refused. Of the 210 patients tested, 28 had MSI-H tumors. Similar numbers of MSI-H were captured, 14.8% preoperatively and 11% postoperatively. Overall, 88% of the high-risk group had tests, and the protocol caught 11% of MSI-H tumors that would have otherwise been missed. An estimated 3% of colon cancers can be attributed to Lynch syndrome. At least 80% of people with Lynch syndrome develop colorectal cancer, many of them before the age of 50.

MSI is a key factor in several cancers including colorectal, endometrial, ovarian, and gastric cancers. Colorectal cancer studies have demonstrated two mechanisms for MSI occurrence. In both cases, microsatellite insertions and deletions within tumor suppressor gene coding regions result in uncontrolled cell division and tumor growth. As a result of this testing, cancer may be caught earlier and physicians may be more proactive in treatment. The testing should be done before surgery, because a diagnosis may change the course of treatment. Testing after surgery also is beneficial as the knowledge gleaned can affect future care for patients and their families. The study was presented at the American Society of Colon and Rectal Surgeons Annual Scientific Meeting, held May 14-18, 2011, in Vancouver (BC, Canada).

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