Saturday, 29 October 2011
Monday, 24 October 2011
Heriditary colorectal cancers (India)
1. Hereditary Non Polyposis Colorectal Cancer (HNPCC)
HNPCC is a familial syndrome. It essentially means that the probability that one will get some type of cancers (Colon cancer, Rectal cancer, Endometrial cancer, Gastric cancer mainly) is enhanced by several fold higher than a normal person if these type of cancers run in their families for successive generations.
As per the guidelines set by the experts (based on decades of research) one should have a genetic consultation if he/she has
a. Cancer at a relatively young age
most cancers in general and colorectal cancer in particular is a disease of elderly i.e >60 years of age. If you have colorectal cancer below 50 years of age while having a healthy life style, chances are that you might have inherited it from parents. This does not necessarily mean that you have a familial cancer but it is a point to suspect so.
b. You have a family member who suffered or is suffering from cancer
one of the main aspect of hereditary cancer is that they have repetitive nature with respect to relatives. If any of your close blood-relative suffered or is suffering from cancer (mainly Colon cancer, rectal cancer, Endometrial cancer (cancer of the lining of uterus (not cervical cancer which is far more common)) and gastric cancer) and you too suffer from colorectal cancer, you should suspect a familial nature to your disease.
c) You have cancer which is in the right colon.
HNPCC typically has more propensity to have cancers in right colon. If you have cancer in the right colon at the same time has any other factor such as a relative with cancer or you are young, there is a possibility that it is HNPCC.
What should you do if you suspect you have Familial cancer.
There is some relieving information...HNPCC patients tend to have better outcomes than the non HNPCC colorectal patients. There are specific and widely accepted diagnostic tests (viz. Microsatellite Instability or MSI testing) to identify whether your cancer belongs to HNPCC type.
The bad news is that such tests though relatively simple, are not widely available in India outside research laboratories. In my knowledge only 2-3 laboratories in India conduct the MSI testing that too for research purpose.
The main reason, i beleive, that MSI testing is not commercially available is that HNPCC is comparatively rare (6-10% of total colorectal cancer from west, FREQUENCY UNKNOWN in India). As such Colorectal cancer is relatively less (compared to breast cancer, cervix, tongue cancer etc) and HNPCC being a miniscule percentage of this, economies of scale cannot be acheived. Though the tests are simple, the necessary equipments are quite costly for diagnostic laboratories.
In my rough estimate the entire test should not cost more than Rs. 3000 for the MSI testing if it were available commercially.
But one can of course consult their clinicians so that they could send their samples (info given below) to the research laboratories ( i will be updating the list of laboratories performing such tests). There are currently some issues with this format. one is that none of the government run laboratories (where research is done) are authorised to give a service of this kind (from possibly ICMR/IMA/drug comptroller of India etc), hence a fee based service cannot work. There are a few government run research and diagnostic laboratories (my parental organization CDFD is one among them) authorised to give molecular diagnostics services. But most of them are not conducting the MSI testing either due to lack of skilled manpower in the diagnostic divisions or due to the lack of people seeking such services. But i am very hopeful a couple of them might come up in very near future on fee-based service.
This directs one to a research based service.
This means you are a volunteer to a research (fortunately atleast 3 teams in India are researching on familial cancers i will update a list soon).
Your clinician will have to guide you through this.
You have to give a consent form clearly stating that you are aware of what research you are volunteering, and you cannot claim monetary or any other benefits from the research outcome. You have to also affirm that you didnot undergo any procedure solely for the research (that is the research is to be done on biopsy/resection performed by your hospital to your cure earlier in the hospital). Normally good hospitals preserve the tissue specimen in paraffin blocks (which is called FFPE blocks) and one can access those specimen for years. The MSI testing is heavily dependent on these blocks and how well they were prepared. so if the hospital procedures are not good it might fail. upto 2-3 years post surgery the blocks could be used for MSI (provided the preparation of blocks were good). Your clinician will have to send the blocks corresponding to the TUMOR and NORMAL margin.
Since the research laboratories are not bound by any legal necessities to give you any feed back at all, you cannot ask them to perform the tests and give it in a stipulated time. It has to be solely based on request and not by authority.
I agree that this is a sad state of affairs, but that is all what one can do. But believing in positive side of humanity one can expect the results in 2-3 weeks, if the researchers agree. The researchers will surely want your family inheritance profile, and they would want you to consent for the data to published in public domain (at the same time keeping your details to identify you anonymous)
Also please be advised that there are no legal framework or guidelines for such a methodology yet. the researchers are bound by ethical rules which states that the volunteers cannot be lured for any sort of benefit at all (and the result of testing may be construed as a benefit). Also privacy of medical aspects of volunteers is absolute must in research, and revealing them is criminal offense (secrecy of information clause). So if you are heading this way clearly understand the complications in such mode, and be patient and tolerant to the research teams.
What next if you know you could get MSI testing done
An MSI test positive (in technical jargon MSI-High) indicates that there is high probability of a family history of tumor of HNPCC type. But this test doesnot confirm that you have HNPCC cancer. Yet the result of MSI has its own implication. This will indicate (if you are lucky enough to get the results in time) that you may have to be treated differently unlike other colorectal patients. Unfortunately here again many clinicians are unaware/unsure of the molecular approach to therapy. But there are quite a few who are well versed in this approach and many tertiary centres have dedicated clinicians for molecular therapy. Also this could mean that you have a better chance of surviving cancer than others with colon cancer. Also since HNPCC is familial your immediate relatives can be advised to be cautious for any signs of cancer or to undergo consultation with doctors in regular intervel (mind you MSI will not confirm the familial nature, but you could be safe than sorry). Recurrence in same patient is also common so be a more vigilant on these aspects and may alter unhealthy lifestyle.
To confirm the MSI testing a rather elaborate procedure is to be performed. There are diagnostic markers (typically Immunohistochemistry) which can identify the faulty gene (inheritance factor) which triggered your tumor initiation. Once the gene is identified, gene sequencing from your blood can be performed to pinpoint the region where the gene is faulty (which is referred as mutation). if you could identify the faulty region of the gene, by gene sequencing you can confirm that you have HNPCC
These last methods are typically very costly and as per my estimate the first time confirmation of HNPCC might cost you atleast 20-30 thousand rupees. But if you are volunteer in a research project you may get to know the mutation free of cost, but as i mentioned above, there is no guarantee that your mutation will be identified nor is it a great way to go.
What if you come to know you are HNPCC patient
As a disclaimer i will forewarn you that knowing own fate is not a pleasing experience. Nothing can be done to correct the faulty genes in your body (with the current technology, though in distant future such methods might be developed). But so is the case if you had only one functional kidney or you had AMD (a degenerative disease with progressive loss of vision). But keeping a positive life to what ever available makes a difference. By knowing that you are HNPCC patient you are just informed about a proability of you to develop cancer and not a certainty. It infact helps you by which you can have your efforts to stay cancer free. Each and every one has a probability to develop cancer and it is only that you have a bit more probabilty. It is like if you are a driver...every traveller has a chance to die of accident but a regular driver has more chance.
If you come to know you are an HNPCC patient that implies that your relatives are also having risk of cancer so is the case with your children or next generation. But by knowing that you have HNPCC you can be cautious with your health and be watchful for any signs of cancer. You can also get your relatives checked for the presence of faulty gene and who ever inherited the faulty gene could be advised to be cautious and to undergo annual colon checkups. Such checks can identify any dangerous development early, and early identification is the best available way for fighting cancer. Also different treatment could be opted if unfortunately any of relatives develop cancer. A healthy lifestyle habit can keep cancer to some extend at bay.
Familial cancers tend to strike very early in life i.e 20-30 years. Loss of life at this age will be traumatic for the rest of family members. But screening may be helpful in identifying cancers early (and could be cured completely by surgery). The risk of developing cancer is quite high in HNPCC if you inherit a faulty gene (50-80% of the persons inheriting the faulty gene might develop cancer, depending on the nature of mutation)
But from a common man's view point HNPCC is nothing specifically bad. Every human is destined to die and ones natural death is largely dependent on the inheritance. Almost all of us have one or the other faulty genes (ranging from simple vitiligo (patchy white areas in skin) to diabetics to cancer). So if you have cancer donot be depressed that you are cursed, but be informed that you have a little bit severe defect than others (i.e none are holier than thou).
Also as a molecular biologist i will like to assure you that molecular medicine is undergoing revolutions. In future we may have cures also available.
If you or any one of your relative is suffering from HNPCC or Colorectal cancer I wish you speedy recovery and a cancer free life for rest of life.
If you have any comments, suggestion or queries please do put it up to me...I can try to help you with whatever limited knowledge i have in this.
regards,
Ratheesh. R
Laboratory of Molecular oncology
Centre for DNA Fingerprinting and Diagnostics
Hyderabad.
HNPCC is a familial syndrome. It essentially means that the probability that one will get some type of cancers (Colon cancer, Rectal cancer, Endometrial cancer, Gastric cancer mainly) is enhanced by several fold higher than a normal person if these type of cancers run in their families for successive generations.
As per the guidelines set by the experts (based on decades of research) one should have a genetic consultation if he/she has
a. Cancer at a relatively young age
most cancers in general and colorectal cancer in particular is a disease of elderly i.e >60 years of age. If you have colorectal cancer below 50 years of age while having a healthy life style, chances are that you might have inherited it from parents. This does not necessarily mean that you have a familial cancer but it is a point to suspect so.
b. You have a family member who suffered or is suffering from cancer
one of the main aspect of hereditary cancer is that they have repetitive nature with respect to relatives. If any of your close blood-relative suffered or is suffering from cancer (mainly Colon cancer, rectal cancer, Endometrial cancer (cancer of the lining of uterus (not cervical cancer which is far more common)) and gastric cancer) and you too suffer from colorectal cancer, you should suspect a familial nature to your disease.
c) You have cancer which is in the right colon.
HNPCC typically has more propensity to have cancers in right colon. If you have cancer in the right colon at the same time has any other factor such as a relative with cancer or you are young, there is a possibility that it is HNPCC.
What should you do if you suspect you have Familial cancer.
There is some relieving information...HNPCC patients tend to have better outcomes than the non HNPCC colorectal patients. There are specific and widely accepted diagnostic tests (viz. Microsatellite Instability or MSI testing) to identify whether your cancer belongs to HNPCC type.
The bad news is that such tests though relatively simple, are not widely available in India outside research laboratories. In my knowledge only 2-3 laboratories in India conduct the MSI testing that too for research purpose.
The main reason, i beleive, that MSI testing is not commercially available is that HNPCC is comparatively rare (6-10% of total colorectal cancer from west, FREQUENCY UNKNOWN in India). As such Colorectal cancer is relatively less (compared to breast cancer, cervix, tongue cancer etc) and HNPCC being a miniscule percentage of this, economies of scale cannot be acheived. Though the tests are simple, the necessary equipments are quite costly for diagnostic laboratories.
In my rough estimate the entire test should not cost more than Rs. 3000 for the MSI testing if it were available commercially.
But one can of course consult their clinicians so that they could send their samples (info given below) to the research laboratories ( i will be updating the list of laboratories performing such tests). There are currently some issues with this format. one is that none of the government run laboratories (where research is done) are authorised to give a service of this kind (from possibly ICMR/IMA/drug comptroller of India etc), hence a fee based service cannot work. There are a few government run research and diagnostic laboratories (my parental organization CDFD is one among them) authorised to give molecular diagnostics services. But most of them are not conducting the MSI testing either due to lack of skilled manpower in the diagnostic divisions or due to the lack of people seeking such services. But i am very hopeful a couple of them might come up in very near future on fee-based service.
This directs one to a research based service.
This means you are a volunteer to a research (fortunately atleast 3 teams in India are researching on familial cancers i will update a list soon).
1) Dr. Devendra Desai -Consultant Gastroenterologist, DNB (Gastroenterology), MD (Gen Med), MBBS - PD Hinduja Hospitals, Mumbai.
2) Dr. T Rajkumar -SCIENTIFIC DIRECTOR, MOLECULAR ONCOLOGY, WIA Cancer Institute, Adayar, Chennai.
3)Ravindran Ankathil, Ph.D - Regional Cancer Centre, Trivandrum.
http://rcctvm.org/raviankathil.htmYour clinician will have to guide you through this.
You have to give a consent form clearly stating that you are aware of what research you are volunteering, and you cannot claim monetary or any other benefits from the research outcome. You have to also affirm that you didnot undergo any procedure solely for the research (that is the research is to be done on biopsy/resection performed by your hospital to your cure earlier in the hospital). Normally good hospitals preserve the tissue specimen in paraffin blocks (which is called FFPE blocks) and one can access those specimen for years. The MSI testing is heavily dependent on these blocks and how well they were prepared. so if the hospital procedures are not good it might fail. upto 2-3 years post surgery the blocks could be used for MSI (provided the preparation of blocks were good). Your clinician will have to send the blocks corresponding to the TUMOR and NORMAL margin.
Since the research laboratories are not bound by any legal necessities to give you any feed back at all, you cannot ask them to perform the tests and give it in a stipulated time. It has to be solely based on request and not by authority.
I agree that this is a sad state of affairs, but that is all what one can do. But believing in positive side of humanity one can expect the results in 2-3 weeks, if the researchers agree. The researchers will surely want your family inheritance profile, and they would want you to consent for the data to published in public domain (at the same time keeping your details to identify you anonymous)
Also please be advised that there are no legal framework or guidelines for such a methodology yet. the researchers are bound by ethical rules which states that the volunteers cannot be lured for any sort of benefit at all (and the result of testing may be construed as a benefit). Also privacy of medical aspects of volunteers is absolute must in research, and revealing them is criminal offense (secrecy of information clause). So if you are heading this way clearly understand the complications in such mode, and be patient and tolerant to the research teams.
What next if you know you could get MSI testing done
An MSI test positive (in technical jargon MSI-High) indicates that there is high probability of a family history of tumor of HNPCC type. But this test doesnot confirm that you have HNPCC cancer. Yet the result of MSI has its own implication. This will indicate (if you are lucky enough to get the results in time) that you may have to be treated differently unlike other colorectal patients. Unfortunately here again many clinicians are unaware/unsure of the molecular approach to therapy. But there are quite a few who are well versed in this approach and many tertiary centres have dedicated clinicians for molecular therapy. Also this could mean that you have a better chance of surviving cancer than others with colon cancer. Also since HNPCC is familial your immediate relatives can be advised to be cautious for any signs of cancer or to undergo consultation with doctors in regular intervel (mind you MSI will not confirm the familial nature, but you could be safe than sorry). Recurrence in same patient is also common so be a more vigilant on these aspects and may alter unhealthy lifestyle.
To confirm the MSI testing a rather elaborate procedure is to be performed. There are diagnostic markers (typically Immunohistochemistry) which can identify the faulty gene (inheritance factor) which triggered your tumor initiation. Once the gene is identified, gene sequencing from your blood can be performed to pinpoint the region where the gene is faulty (which is referred as mutation). if you could identify the faulty region of the gene, by gene sequencing you can confirm that you have HNPCC
These last methods are typically very costly and as per my estimate the first time confirmation of HNPCC might cost you atleast 20-30 thousand rupees. But if you are volunteer in a research project you may get to know the mutation free of cost, but as i mentioned above, there is no guarantee that your mutation will be identified nor is it a great way to go.
What if you come to know you are HNPCC patient
As a disclaimer i will forewarn you that knowing own fate is not a pleasing experience. Nothing can be done to correct the faulty genes in your body (with the current technology, though in distant future such methods might be developed). But so is the case if you had only one functional kidney or you had AMD (a degenerative disease with progressive loss of vision). But keeping a positive life to what ever available makes a difference. By knowing that you are HNPCC patient you are just informed about a proability of you to develop cancer and not a certainty. It infact helps you by which you can have your efforts to stay cancer free. Each and every one has a probability to develop cancer and it is only that you have a bit more probabilty. It is like if you are a driver...every traveller has a chance to die of accident but a regular driver has more chance.
If you come to know you are an HNPCC patient that implies that your relatives are also having risk of cancer so is the case with your children or next generation. But by knowing that you have HNPCC you can be cautious with your health and be watchful for any signs of cancer. You can also get your relatives checked for the presence of faulty gene and who ever inherited the faulty gene could be advised to be cautious and to undergo annual colon checkups. Such checks can identify any dangerous development early, and early identification is the best available way for fighting cancer. Also different treatment could be opted if unfortunately any of relatives develop cancer. A healthy lifestyle habit can keep cancer to some extend at bay.
Familial cancers tend to strike very early in life i.e 20-30 years. Loss of life at this age will be traumatic for the rest of family members. But screening may be helpful in identifying cancers early (and could be cured completely by surgery). The risk of developing cancer is quite high in HNPCC if you inherit a faulty gene (50-80% of the persons inheriting the faulty gene might develop cancer, depending on the nature of mutation)
But from a common man's view point HNPCC is nothing specifically bad. Every human is destined to die and ones natural death is largely dependent on the inheritance. Almost all of us have one or the other faulty genes (ranging from simple vitiligo (patchy white areas in skin) to diabetics to cancer). So if you have cancer donot be depressed that you are cursed, but be informed that you have a little bit severe defect than others (i.e none are holier than thou).
Also as a molecular biologist i will like to assure you that molecular medicine is undergoing revolutions. In future we may have cures also available.
If you or any one of your relative is suffering from HNPCC or Colorectal cancer I wish you speedy recovery and a cancer free life for rest of life.
If you have any comments, suggestion or queries please do put it up to me...I can try to help you with whatever limited knowledge i have in this.
regards,
Ratheesh. R
Laboratory of Molecular oncology
Centre for DNA Fingerprinting and Diagnostics
Hyderabad.
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