Mary Claire King visited the Indian Institute of Science as part of the 'Cell-TNQ India Distinguished Lectures Series' and her lecture just blew me away.
We start with a brief introduction of this amazing scientist who has literally changed the world in more ways than one. A Berkeley educated geneticist, King proved for the first time that humans and chimpanzees are 99% genetically identical, giving weight to the theory that the two species diverged only about 5 million years ago, a view that was not very popular at that time. She is responsible for discovering the BRCA 1 and the BRCA 2 genes and announcing to the world that cancers like breast and ovarian cancers can be hereditary. She is also known for her human rights initiatives. She joined the protesting grandmothers in Argentina, whose grandkids and kids had been taken from them by the regime and were forced to live with military families. Her work in genetic forensics provided irrefutable evidence that has since helped thousands across the world.
Now this is important: I am not a geneticist, my formal links with classroom biology were severed in high school, so inspite of King's wonderful talk the content that follows is my understanding of the talk, which may be inaccurate at several points.
Okay so here goes,
Breast and Ovarian cancer have been dubbed as the disease of the educated and the disease of the rich. We know for a fact that human females are the most evolved organisms to have roamed the face of this planet, unfortunately they seem to have become victims of their own advancement.
One might wonder why did evolution not take care of curing cancer, by natural selection for healthier indivisuals? The answer lies in the fact that both breast and ovarian cancers are post reproductive, thus escaping the scrutiny of evolution.
The risk of breast and ovarian cancer is directly proportional to the gap between the age women start menstruating and the age at which they have their first pregnancy. Who knew!
Menstruation starts when estrogen (the female hormone) hits a certain level in the body. Interestingly the production of estrogen in the body is related to the body mass index (BMI) (defined as the body mass divided by the square of the body height).
As families start to become more educated and are more well to do, young women are hitting the BMI threshold earlier (as they have access to better diets), therefore we see young women hitting puberty much earlier, the age has progressively lowered from 18 to 16 to now around 11.
At the same time women are making an active choice of putting their carriers first and choosing to start a family at a much later age. Thus increasing the gap.
This phenomena is highly correlated with the how well to do the society in which they live are. In the past Europe and the US have been the primary victims of these cancers but as the developing world catches up to the developed world it inherits their problems too.
Studies show that the cases of breast cancer in Indian cities are growing at an exponential rate.
If you are looking for an interesting read check out The race to clone BRCA1 in 'Science', which documents the fascinating story of discovering the gene.
Dr King's work shows that individuals who have a BRCA1 or BRCA2 gene mutation are at a very high risk of developing breast or ovarian cancer. Infact these people have an 80% chance of developing these cancers over their lifetimes. 80%. Let that sink in.
But my mother and grandmother did not have these issues!
It is not just the women!
BRCA 1 and BRCA 2 can be inherited from the paternal side too. Also men carrying these genes are predisposed to developing prostate cancer in their lifetimes. [The new England Journal reports that 15% of patients suffering from prostate cancer have a BRCA-2 mutation]
THE SOLUTION
Knowing what we know how can we help ourselves? The answer is early testing for these genes. The BROCA gene panel can be used to conduct a simple sequencing which costs about $225. If the patient is a carrier of the either the BRCA 1 or BRCA 2 gene then Dr King recommends a salpio oophorectomy around the age of 35-40 i.e. the surgical removal of the ovaries and fallopian tubes to lower the estrogen levels in the body. This will significantly reduce the risk of both breast and ovarian cancer. PARP inhibitors have also know to be helpful.
We start with a brief introduction of this amazing scientist who has literally changed the world in more ways than one. A Berkeley educated geneticist, King proved for the first time that humans and chimpanzees are 99% genetically identical, giving weight to the theory that the two species diverged only about 5 million years ago, a view that was not very popular at that time. She is responsible for discovering the BRCA 1 and the BRCA 2 genes and announcing to the world that cancers like breast and ovarian cancers can be hereditary. She is also known for her human rights initiatives. She joined the protesting grandmothers in Argentina, whose grandkids and kids had been taken from them by the regime and were forced to live with military families. Her work in genetic forensics provided irrefutable evidence that has since helped thousands across the world.
 |
| Dr King at the JN Tata auditorium |
Now this is important: I am not a geneticist, my formal links with classroom biology were severed in high school, so inspite of King's wonderful talk the content that follows is my understanding of the talk, which may be inaccurate at several points.
Okay so here goes,
Breast and Ovarian cancer have been dubbed as the disease of the educated and the disease of the rich. We know for a fact that human females are the most evolved organisms to have roamed the face of this planet, unfortunately they seem to have become victims of their own advancement.
One might wonder why did evolution not take care of curing cancer, by natural selection for healthier indivisuals? The answer lies in the fact that both breast and ovarian cancers are post reproductive, thus escaping the scrutiny of evolution.
The risk of breast and ovarian cancer is directly proportional to the gap between the age women start menstruating and the age at which they have their first pregnancy. Who knew!
Menstruation starts when estrogen (the female hormone) hits a certain level in the body. Interestingly the production of estrogen in the body is related to the body mass index (BMI) (defined as the body mass divided by the square of the body height).
As families start to become more educated and are more well to do, young women are hitting the BMI threshold earlier (as they have access to better diets), therefore we see young women hitting puberty much earlier, the age has progressively lowered from 18 to 16 to now around 11.
At the same time women are making an active choice of putting their carriers first and choosing to start a family at a much later age. Thus increasing the gap.
This phenomena is highly correlated with the how well to do the society in which they live are. In the past Europe and the US have been the primary victims of these cancers but as the developing world catches up to the developed world it inherits their problems too.
Studies show that the cases of breast cancer in Indian cities are growing at an exponential rate.
 |
| The graph looks like this, this is not the original graph just a py plot simulation |
If you are looking for an interesting read check out The race to clone BRCA1 in 'Science', which documents the fascinating story of discovering the gene.
Dr King's work shows that individuals who have a BRCA1 or BRCA2 gene mutation are at a very high risk of developing breast or ovarian cancer. Infact these people have an 80% chance of developing these cancers over their lifetimes. 80%. Let that sink in.
 |
| Complex Structure of the BRCA1 RING domain and BARD1 RING domain credit: By Emw - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8763313 |
But my mother and grandmother did not have these issues!
It is not just the women!
BRCA 1 and BRCA 2 can be inherited from the paternal side too. Also men carrying these genes are predisposed to developing prostate cancer in their lifetimes. [The new England Journal reports that 15% of patients suffering from prostate cancer have a BRCA-2 mutation]
THE SOLUTION
Knowing what we know how can we help ourselves? The answer is early testing for these genes. The BROCA gene panel can be used to conduct a simple sequencing which costs about $225. If the patient is a carrier of the either the BRCA 1 or BRCA 2 gene then Dr King recommends a salpio oophorectomy around the age of 35-40 i.e. the surgical removal of the ovaries and fallopian tubes to lower the estrogen levels in the body. This will significantly reduce the risk of both breast and ovarian cancer. PARP inhibitors have also know to be helpful.
If there is one thing that you take away from this post let it be this: get yourself and your loved ones tested for the BRCA 1 and 2 genes. It is just $225 test which can change your life.
"Every breast or ovarian cancer patient with a BRCA1 or BRCA2 mutation detected after diagnosis is a missed opportunity to prevent cancer. "
 |
| Thank you Dr King! |
Update:
Dr Priya Mathur, a PhD holder in Biochemistry & Molecular Genetics from the University of Chicago weighed in with the following advice:
My concern with advocating for BRCA testing for the general population is that it can lull people into a false sense of security. It is critical that those with a family history of BRCA-mutant cancers be tested because these mutations drive an aggressive form of hereditary cancer and steps can be taken to prevent it. However, the vast majority of breast cancer is sporadic, or non-hereditary, which means that even with a negative BRCA test result, a person carries the risk of developing sporadic breast cancer. Early detection via routine screening is the best way to improve outcomes, BRCA1/2 screening is not a substitute for routine mammography and self-screening. |
Thanks for writing and highlighting the way to prevent these cancers...normally screening is widely promoted for breast cancer but that only detects cancer when it has already manifested!!!
ReplyDeleteYes! Hopefully awareness in India grows at the rapid rate we need it to, that is our best chance to fight these cancers.
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