After the Test
14/05/13 16:26 Filed in: GenomeWeb Daily Scan
Submitted by S. Pelech - Kinexus on Tue, 05/14/2013 - 15:05
Angelina Jolie's highly publicized decision to have radical surgery based on the presence of a mutation in her BRCA1 gene is a preview of what is likely to become more common place in the future with companies that are pushing genetic testing. In general, woman have about a 1 in 9 chance of developing breast cancer in their life-time, and roughly 2.2% of breast tumours have a point mutation, deletion or insertion in their BRCA1 gene. Running the numbers, this indicates that in the general female population in the United States alone, over a third of a million women (156 million / 9 x 0.022= 382,333) would undergo similar surgery if they followed the advice of Ms. Jolie and her doctors.
Full blown cancer arises from multiple mutations that coincide within exactly the same genome on different genes that can complement each other to promote the disease. The BRCA1 gene encodes a tumour suppressor protein (TSP), which can loose its functionality when it is mutated. TSP's commonly act to block cell growth and division, essentially acting as brakes on cancer. Much of the human population is likely born with compromising mutations in one or more of probably more than a hundred different TSP genes that we know of today. The real problem arises when additional mutations accumulate during a person's lifetime with exposure to chemical carcinogens and radiation. In particular, driver mutations in oncogenes can lead to a gain of function in the proteins that they encode, which can facilitate the growth and spreading of tumours. Our knowledge of the number of tumour suppressor genes and oncogenes is slowing improving with current cancer research and we are starting to identify the specific mutations that are the most problematic. However, this knowledge is still pretty rudimentary. Consequently, it is really hard to assign specific probabilities for the development of cancer based on the analysis of just a couple of genes for the whole population, never mind for a single individual.
Other tumour suppressor genes are actually much more commonly mutated in human cancers than BRCA1 or BRCA2. For example, the p53 and RB1 genes are mutated in about 29.8% and 4.7%, respectively, in all human tumours. In breast cancer specifically, p53 and RB1, respectively, are mutated 23% and 3.9% of the time. By contrast, BRCA1 and BRCA2 mutations show up in only 2.2% and 1.3% of human breast tumours. Testing for especially common or highly risky cancer-driver mutations can certainly alert individuals that are at higher risk to have more frequent check ups and actually test for the presence of cancer, and the prognosis is much better with earlier diagnosis. Moreover, adopting a healthier life-style can cut the risk of cancer by approximately half.
The decision to have a preventive double mastectomy without evidence of actual breast cancer is obviously a personal choice with benefits and consequences. Epidemiology studies have indicated that breast cancer survival rates from lumpectomies are as high as full mastectomies. Careful monitoring for breast cancer, for example, with highly sensitive proteomics-based tests and imaging can provide very early diagnosis with better patient outcomes. In view of how common many disease-related mutations may actually be within our population, it is critical that tests for these mutations put the risks into perspective and radical solutions are not taken unnecessarily. With the remarkable advancements in modern medicine, it is worth considering that deadly diseases today, could become relatively minor or at least manageable problems in the near future.
Link to the original blog post
Angelina Jolie's highly publicized decision to have radical surgery based on the presence of a mutation in her BRCA1 gene is a preview of what is likely to become more common place in the future with companies that are pushing genetic testing. In general, woman have about a 1 in 9 chance of developing breast cancer in their life-time, and roughly 2.2% of breast tumours have a point mutation, deletion or insertion in their BRCA1 gene. Running the numbers, this indicates that in the general female population in the United States alone, over a third of a million women (156 million / 9 x 0.022= 382,333) would undergo similar surgery if they followed the advice of Ms. Jolie and her doctors.
Full blown cancer arises from multiple mutations that coincide within exactly the same genome on different genes that can complement each other to promote the disease. The BRCA1 gene encodes a tumour suppressor protein (TSP), which can loose its functionality when it is mutated. TSP's commonly act to block cell growth and division, essentially acting as brakes on cancer. Much of the human population is likely born with compromising mutations in one or more of probably more than a hundred different TSP genes that we know of today. The real problem arises when additional mutations accumulate during a person's lifetime with exposure to chemical carcinogens and radiation. In particular, driver mutations in oncogenes can lead to a gain of function in the proteins that they encode, which can facilitate the growth and spreading of tumours. Our knowledge of the number of tumour suppressor genes and oncogenes is slowing improving with current cancer research and we are starting to identify the specific mutations that are the most problematic. However, this knowledge is still pretty rudimentary. Consequently, it is really hard to assign specific probabilities for the development of cancer based on the analysis of just a couple of genes for the whole population, never mind for a single individual.
Other tumour suppressor genes are actually much more commonly mutated in human cancers than BRCA1 or BRCA2. For example, the p53 and RB1 genes are mutated in about 29.8% and 4.7%, respectively, in all human tumours. In breast cancer specifically, p53 and RB1, respectively, are mutated 23% and 3.9% of the time. By contrast, BRCA1 and BRCA2 mutations show up in only 2.2% and 1.3% of human breast tumours. Testing for especially common or highly risky cancer-driver mutations can certainly alert individuals that are at higher risk to have more frequent check ups and actually test for the presence of cancer, and the prognosis is much better with earlier diagnosis. Moreover, adopting a healthier life-style can cut the risk of cancer by approximately half.
The decision to have a preventive double mastectomy without evidence of actual breast cancer is obviously a personal choice with benefits and consequences. Epidemiology studies have indicated that breast cancer survival rates from lumpectomies are as high as full mastectomies. Careful monitoring for breast cancer, for example, with highly sensitive proteomics-based tests and imaging can provide very early diagnosis with better patient outcomes. In view of how common many disease-related mutations may actually be within our population, it is critical that tests for these mutations put the risks into perspective and radical solutions are not taken unnecessarily. With the remarkable advancements in modern medicine, it is worth considering that deadly diseases today, could become relatively minor or at least manageable problems in the near future.
Link to the original blog post