Researchers develop personalized medicine tool for inherited colorectal cancer syndrome

An international team of researchers led by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) has developed, calibrated, and validated a novel tool for identifying the genetic changes in Lynch syndrome genes that are likely to be responsible for causing symptoms of the disease. The results were published this week in the journal Genetics in Medicine.

Lynch syndrome is a hereditary condition that results in higher rates of colon, endometrial, and other cancers. If unmanaged, individuals with Lynch syndrome have a 75 percent lifetime risk of developing colorectal cancer. It is believed that approximately five percent of all colorectal cancer cases are associated with this syndrome.

Millions of distinct changes are possible in genes that control health, and it is a massive undertaking to identify which specific changes are associated with developing disease. Some genetic changes are believed to have no impact at all, while others carry significant risk.

Researchers at Huntsman Cancer Institute work to understand and classify which gene changes are likeliest to cause disease, as well as to identify appropriate strategies to help manage disease risk.

This groundbreaking study was led by Sean Tavtigian, Ph.D., a cancer researcher at HCI and professor of oncological sciences at the U of U. The work was built on a decade-long international collaboration. “Correctly identifying which of the genetic changes we observe actually result in disease is fundamentally important in clinical care,” said Tavtigian. “Having clarity on this issue has the potential to add years to patients’ lives, reduce anxiety about disease risk, and use health care dollars more efficiently.”

The team used a laboratory test previously developed by the group of Niels de Wind, Ph.D., associate professor of human genetics at the Leiden University Medical Center in The Netherlands, to characterize genetic changes associated with disease risk. The lab test, called the Cell-free in vitro MMR Activity (CIMRA) assay, improves classification of variants of uncertain significance in Lynch syndrome. “The test is rapid and accurate,” said de Wind. In the current study, the test was thoroughly calibrated and validated, such that its results could now be integrated with computer-based modeling and clinical data. As a result, this study provides an analytical tool suitable for clinical use to assess the potential of changes in Lynch syndrome genes to cause disease.

“A key point is that we believe the accuracy of the tool combining the CIMRA test with the previously published computational analysis to be about 97 percent, making it appropriate for clinical use,” said Tavtigian. de Wind added that the work “represents a new pinnacle in the classification of genetic variation.”

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Type 2 diabetes linked to colorectal cancer risk in men

(HealthDay)—Type 2 diabetes (T2D) is associated with an increased risk for colorectal cancer (CRC), with the association significant for men only, according to a study published online Nov. 7 in the British Journal of Cancer.

Yanan Ma, from China Medical University in Shenyang, and colleagues followed 87,523 women from the Nurses’ Health Study and 47,240 men from the Health Professionals Follow-up Study to examine the correlation of T2D and its duration with the risk for incident CRC.

The researchers documented 3,000 cases of CRC during a follow-up of 32 years. Among men, the risk for CRC was increased for those with versus those without T2D (hazard ratio, 1.42; 95 percent confidence interval, 1.12 to 1.81). The positive association remained in sensitivity analyses excluding CRC identified within one year of diabetes diagnosis and excluding patients with T2D using hypoglycemic medications. Among women, there was a positive but not statistically significant association between T2D and CRC risk (hazard ratio, 1.17; 95 percent confidence interval, 0.98 to 1.39).

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