Colorectal cancer gene found

April 19, 2016

???Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study??? is the first large linkage study of families with CRC and colon polyps in the country. Because only five percent of CRC cases are due to known gene defects, this NIH-funded study is designed to identify the remaining CRC-related susceptibility genes. The team built on a previous study which identified a specific region on chromosome 9q that harbors a CRC susceptibility gene. Upon review of a whole genome scan of all chromosome pairs in 194 families, the researchers were able to identify additional CRC gene regions on chromosomes 1p, 15q, and 17p.

While the overall Case Western Reserve University School of Medicine study looked at families with colon cancer and colon polyps, the study also analyzed families with different clusters of cancer, such as CRC with multiple polyps and CRC with breast cancer. These different phenotypes appeared to link to different chromosomal regions, which the study teams says supports the idea of multiple susceptibility genes causing different types of cancers. These links will be further investigated in the next phase of the study.

???The goal of our study is to identify the CRC genes in susceptible patients to better understand who may be prone to develop CRC and why,??? said Georgia L. Wiesner, M.D., lead author of ???Identification of Susceptibility Genes for Cancer in a Genome-wide Scan: Results from the Colon Neoplasia Sibling Study.??? ???This study is step towards future the of genetic CRC testing.???

The genome-wide scan used in this study will help physicians elucidate the genetic factors in CRC in the future. Once the genes are identified, physicians will be able to use these genetic markers to identify ???at risk??? patients and to develop better cancer screening strategies, such as colonoscopies well before standard screening begins at age 50. Currently, without new gene tests, family history is the only tool to determine a person's risk for CRC. Knowing the exact gene will allow physicians to better take care of CRC patients and lead to earlier screening.

case/

The researchers noted that the drug combination would likely be well tolerated because it did not cause excessive bleeding in the mice, as might be expected from platelet inhibitors. The research group plans to continue to study the process of metastasis and the role played by platelets.

In collaboration with Michael Naughton, M.D., assistant professor of medicine, Weilbaecher is also involved in a clinical trial of women with advanced breast cancer to test aspirin and Plavix?®, another antiplatelet drug, to see if the drug combination affects the number of tumor cells that circulate in the blood. The trial is open only to breast cancer patients undergoing treatment at the Siteman Cancer Center.

Ulu?§kan ?–, Eagleton MC, Floyd DH, Morgan EA, Hirbe AC, Kramer M, Dowland N, Prior JL, Piwnica-Worms D, Jeong SS, Chen R, Weilbaecher K. APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice. Journal of Cellular Biochemistry, Feb. 7, 2008 (advance online publication).

Funding from National Institutes of Health, the Ewing Marion Kauffman Foundation, the Barnes-Jewish Hospital Foundation and Washington University supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Siteman Cancer Center is the only federally-designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine. Siteman has satellite locations in West County and St. Peters, in addition to its full-service facility at Washington University Medical Center on South Kingshighway.

wustl/