Genetic Mutation Linked To Breast, Ovarian Cancer Underestimated?

2002 JAN 10 - (NewsRx.com & NewsRx.net) -- Mutations in key genes that could make some women more susceptible to breast and ovarian cancer may be more widespread than researchers had previously believed.

These findings from a new multinational study have broad implications for both clinical cancer geneticists and their patients.

The research, which appeared in the December 11, 2001, issue of the Journal of Medical Genetics, compared four different methods to determine which one most accurately revealed mutations in large genes like BRCA1 and BRCA2, two genes that are strongly linked to the development of breast and ovarian cancer. Investigators hoped the study would provide an objective basis for interpreting genetic epidemiological research that had used the four mutation detection techniques.

Scientists have demonstrated that women with mutations in the BRCA1 and BRCA2 genes have a lifetime risk of breast cancer between 56% - 87%, and a lifetime risk of ovarian cancer between 27-44%. Epidemiological research has previously suggested that fewer than about 5% of women who have isolated breast cancer carry such mutations.

But the new study, led by senior authors Dr. Charis Eng, director of the Clinical Cancer Genetics Program at The Ohio State University, and Dr. Tom S. Frank of Myriad Genetic Laboratories in Salt Lake City, Utah, suggests that figure may be too low, primarily due to less than perfect genetic scanning methods.

"The most accurate way to detect genetic mutations is through a process called direct nucleotide sequence analysis," says Eng, "but that method is also the most expensive and the most labor intensive, so many laboratories involved in broad-based, epidemiological research with BRCA1 and BRCA2 often use other means that are quicker and cheaper."

To find out how those other methods compare to direct gene sequencing, the research team, which worked under the auspices of the Breast Cancer Information Core, assembled a set of 65 blinded samples containing 58 distinct BRCA1 mutations, and sent them to four different research laboratories in the United States (Dr. Jan Vijg, University of Texas Health Science Center; Dr. Elaine Ostrander, Fred Hutchinson Cancer Research Center, Seattle), the Netherlands (the University of Leiden) and Austria (Dr. Teresa Wagner, University of Vienna). Each lab, which was expert in its respective gene scanning technology, searched for genetic mutations previously identified by direct gene sequencing using one of the following scanning methods: single strand conformational polymorphism analysis (SSCP), conformation-sensitive gel electrophoresis (CSGE), two dimensional gene scanning ...