The results of the study, which are being presented today at the annual American Society of Clinical Oncology meeting, also provide the strongest evidence to date that this surgery significantly reduces the overall risk of BRCA-associated breast and ovarian cancers.

"These findings will help doctors to better counsel women who have an inherited predisposition to ovarian and breast cancers and allow tailoring of risk-reduction strategies depending on what particular mutation a woman has inherited," said the study's lead author Noah D. Kauff, MD, a gynecologist and geneticist at Memorial Sloan-Kettering Cancer Center (MSKCC).

The study followed 886 women over the age of 30 who carry the BRCA1 or BRCA2 genetic mutation. Of this group, 561 opted to have their ovaries and fallopian tubes surgically removed -- a procedure called risk-reducing salpingo-oophorectomy -- while 325 chose to participate in ovarian surveillance. The women were followed for 40 months via questionnaire or medical review.

The results showed that overall the prophylactic surgery reduced the incidence of ovarian and related cancers by 89 percent and decreased breast cancer incidence by 47 percent. When broken down further, the results indicate that none of the women carrying the BRCA2 mutation who had the surgery developed ovarian cancer, while women carrying the BRCA1 mutation who had the surgery decreased their risk of developing ovarian or related cancers by 87 percent.

The study showed that women with BRCA2 mutations also reduced their risk of developing breast cancer by 72 percent, while those with BRCA1 mutations reduced their risk of breast cancer by 39 percent. Why the results of the procedure differ in BRCA1 carriers and BRCA2 carriers is "a question that we are currently exploring and hope to answer in future studies," said Dr. Kauff.

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Ideker's team uncovered a tangled network of interactions of 30 transcription factors with more than 5,000 yeast genes. A transcription factor is a protein that, either alone or in combination with other transcription factors, binds to one or more genes to affect the expression of that gene or genes. The discovery by Ideker's group of a huge network of transcription factor-gene interactions was made possible by new biotechnology tools that provide comprehensive analysis of cells, like a passerby suddenly being able to monitor all the telephone calls made within a city.

The team discovered that part of the interaction network was involved, as expected, in repairing damaged DNA. However, they were surprised to find that a much larger part of the network is involved in modulating the expression of genes not directly related to DNA repair, such as genes involved in cell growth and division, protein degradation, responses to stress, and other metabolic functions. Ideker and others have theorized that when a cell's DNA is damaged, the cell may be programmed to also stop dividing and perform a variety of housekeeping chores while it repairs its DNA. If true, the model may demystify the long-standing question of why DNA damage influences the expression of hundreds of genes not involved in the actual repair process.

"What we quickly realized is that we had uncovered not just a model of DNA repair, but a blueprint of how the initial event of DNA damage is transmitted by these transcription factors to repair processes and all the other important functions of the cell," said Ideker. "With this model now in hand, we'd like to take a much closer look at the cell's response to environmental toxins. We'd like to understand what goes wrong in certain congenital diseases involving DNA repair, and we'd also like to understand how the model plays a role in various cancers."

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