<<Genetic predisposition does not explain an epidemic, which is what breast cancer is at present. There is a cause. Many believe as I do that it is cause by herbicides and pesticide. Doctors, MD's, are not researchers or trained at scientific research. They treat patients. They do not have the time or money for research.>>
You aren't as well informed about this as some doctors & those who have it in their own family or a family with whom they are very closely associated. Please review:
Source: Ohio State University Medical Center (http://www.osumedcenter.edu/)
Date: Posted 12/17/2001
Genetic Mutations Linked To Breast, Ovarian Cancer May Be Underestimated
COLUMBUS, Ohio - Mutations in key genes which 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, appearing in the Dec. 11 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 percent, and a lifetime risk of ovarian cancer between 27-44 percent. Epidemiological research has previously suggested that fewer than about 5 percent 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 (TDGS) and denaturing high performance liquid chromatography (DHPLC).
Only the laboratory using DHPLC correctly identified all of the mutations that had previously been found by direct gene sequencing. The laboratory utilizing TDGS correctly identified 91 percent, and the laboratories using SSCP and CSGE identified 72 percent and 76 percent of the mutations, respectively, but subsequently confirmed and reported only 65 percent and 60 percent of the alterations, respectively. Because of their lower mutation detection rates, the SSCP and CSGE methods failed to identify more than 20 percent of the mutations in the study.
Eng said the "misses" were the result of both administrative errors and inherent weaknesses in the detection methods. This led the authors to conclude that earlier studies may have underestimated the prevalence of BRCA1 mutations.
For example, the authors said a previous study pegging the rate of mutations in BRCA1 alone at 3.3 percent on the basis of SSCP analysis would likely generate a mutation rate closer to 5 percent using a more accurate scanning method. Eng said another study used CSGE to estimate that 16 percent of women attending a hereditary-risk clinic would have mutations in BRCA1. If a more accurate method would have been used, the rate would have been nearly 27 percent.
"Clinical cancer geneticists advise and manage their patients on the basis of these genetic epidemiological tests," says Eng, "so we need and expect the best data possible." The authors say the study has implications for women with a strong family history of cancer and who received negative BRCA1 and BRCA2 test results from research laboratories performing specific studies in the past, or from clinical laboratories using methods such as SSCP and CSGE. They say many of these women may actually carry significant mutations that were not detected due to the limitations of the technology used by those laboratories.
Investigators also looked at the cost of the various alternatives to gene sequence analysis, and found the most accurate one, DHPLC, was also the most expensive.
They added, however, that the cost of the various methods is likely to drop with improved technology, processing and efficiency. The study was partially funded by the National Institutes of Health, the Dutch Cancer Society, and the Ludwig-Boltzmann Institut fuer Experimentelle Onkologie.
Some members of the research team are employed by Myriad Genetic Laboratories, which performs sequence analysis of BRCA1 and BRCA2 on a commercial basis.
sciencedaily.com
* - richard's note - in addition to a rather large population with this mutation in the Netherlands, Finland, it is also seen to a few communities in WI, MN ,& one in samll town the panhandle of TX all in families of Dutch Finish or Jewish extraction.
You might find the note here concerning "prophylactic mastectomy" interesting.
imaginis.com
Here it is noted this mutation FAR higher than would be considered "normal" in a part of the Jewish population:
mgh.harvard.edu
Please note here that this genetic mutation is also seen a causative factor in both prostate & male breast cancer!!!
cancer.duke.edu
Finland:
cee.hw.ac.uk |
