Thank God I do not have to pay for my genes !

 

I was clearly worried last week as the issue of patenting of genes was to be debated the ‘supreme court of USA’.. Clearly it would be a nightmare that as soon as your child is born, you need to pay multiple companies who patented different genes.  Fortunately in their infinite wisdom, the US court has not allowed the patenting of BRCA1 and BRCA2 genes as they naturally occur in human genome discovered by scientists.

This of course raises a large query as to why  the petition to patent human genome, which is a result of millennia of evolution, can be even be considered for legal patenting.  There is also a caveat on some of the synthesized DNA genes that can be patented but one has to see the implication of the same. Let’s not discuss the jurisdiction of US Supreme Court on the gene pool of human race on planet earth.

Clearly science is now moving into more commercialization.  Earlier scientists primarily worked for the sheer joy of finding something exciting and new which was of potential benefit to the society.  Many times it involved sacrifice and only a few were recognized, sometimes after their life, by awards and prizes. Marie Curie who along with her husband has given us an insight into radioactivity, finally succumbed to the harmful activities of radiation which were unknown at that time.

Many of the brilliant scientists  do not have adequate financial returns. But then, somewhere it happened that patenting becomes more important  than publication of scientific results.  In fact, a new findings in science is patented first and published later. It is always not necessary for patenting to lead to commercial exploitation, but it does guarantee intellectual property which is much more important than commercialization. In medical science, financial reward is still not the primary motivation.

Sometimes commercial interest speeds up science.  Craig Venter, the geneticist, started a private funded institution  for unraveling the human genome.  It was a jolt and  many international academic institutions to come together to match  the speed of private enterprise and work on the human genome project and it is interesting that both completed around the same time. 

So coming back to genes in cancer,   one of the associations among the common cancers is colon cancer.  In fact, it was Henry Lynch who identified that some colon cancers are passed through generations, so called ‘Lynch Syndrome’.

There are certain characteristics in those families when it occurs in younger age and it occurs in 2 or more  individuals across 2 generations and if such a history is there we now have a reliable test called microsatellite instability by which the offspring can be detected to have the genetic abnormality in DNA  or not.  HNPCC ( Lynch syndrome) is basically due to a deficient mechanism of DNA repair  in these families.  Surprisingly because of the awareness of the inheritance these patients tend to get checked up more frequently and detected early and they need removal of nearly 80% of the colon to prevent multiple colon cancers from occurring. 

So for  a clinicians treating colon cancer :

If I see a young patient, I have to enquire about the family history and also check the MSI and if it is positive, would offer a subtotal cholectomy or removing 80% of the colon than removing just the affected colon.

 Strong genetic associations are also seen in some families with Eye tumors in children called retinoblastoma but these are rare.  So though the genetic abnormalities leading to cancer are rare, genetic testing would have a far larger implication and should not be patented as in current situation where larger interest of the society is more important than commercial benefit.

Angelina starts an Anxiety wave – Is it warranted? The scientific facts to ‘fight fear of genes’

Sharmila works in our bank as a Relationship Manager. She is a bubbly and cheerful girl around 30 and recently married.

The other day she came to me, panic written all over her face.

“Doctor, I am terrified!!” she said and burst into tears.

I said “Why don’t you just relax and tell me what’s bothering you so much?”

“Doctor, my mother had breast cancer and now I am really scared that I have to undergo bilateral mastectomy (removal of both my breasts) and have implants done to reduce my risk.

Can you recommend someone??!!”

I was taken aback!  I said, “Wait a minute, wait a minute, now why do you have to do this?”

She said, “Angelina Jolie has declared, that’s how she has reduced her risk and I do not know where to get this genetic testing done”

What kind of panic and anxiety must be triggered amongst millions of women across the world by this dramatic revelation of a Hollywood star?

Of course, she has done this with the faith that one has to be cautions (let’s assume that her PR exercise story is not true!)

I thought I would do a bit of research and give the facts to Sharmila and many other ladies who are possibly equally frightened and anxious because of this piece of news.

Is Cancer hereditary?  Particularly is breast cancer hereditary? And are extreme measures like a bilateral mastectomy necessary? If so in whom ?

Let’s get into a bit of science on the rogue genes – BRCA1 and BRCA 2.

They were first identified in families with breast cancer.

If just one relative has breast cancer and it is NOT a familial or hereditary breast cancer. So just a family history of breast cancer does not mean there are inheritable abnormal genes increasing risk of breast cancer

I asked Sharmila, “Apart from your mother does any one in your family have breast cancer?”

She said, “I think my husband’s aunt had some breast problem”

“No No, your relatives by blood line like your mother, maternal grand mother, sisters, maternal aunts etc.”

Sharmila said, “No, I don’t think so”

“Good, then you are NOT in the super high-risk group of hereditary breast cancer. So don’t worry.”

When we look at the scientific data, there are 3 groups of women:

  1. Familial breast cancer – Familial or Hereditary breast cancer or breast ovarian cancer syndrome are defined as those families with 3-4 cases of breast +/- ovarian cancer across two generations.  In these patients also, the genes BRCA1 and BRCA2 are not always responsible.  52% of such cases are due to BRCA1 and 35% are due to BRCA2 and the remaining are due to other genes.

This is the group where testing would be appropriate if ‘they wish to’. If you don’t carry a mutation you can avoid intense surveillance like 6 monthly tests.

However, the problem is, finding a BRCA1 /2 does not mean that you DO get breast Cancer.

The problem of ‘gene expression’ and ‘penetrance’ compound the issue. Not all genes express and produce cancer. But, once you know that you carry the gene, the panic starts. Proportion of breast cancer cases in the general population due to BRCA1 is 5.3% below age 40 years, 2.2% between ages 40 and 49

As doctors we need to be cautious in not triggering anxiety attacks and many have opted out of gene testing and rightly so.

2. The 2nd group consists of those who are diagnosed as having breast cancer.

What is the impact of genetic testing and is it mandatory to do genetic testing?

Not necessary at all.  The reason is that a random genetic testing for any cancer would not really show a mutation.

Fundamentally there are 2 types of cancers (1) Familial or Hereditary (related to abnormalities in genes) and (2) Sporadic or a random occurrence of the disease.

Sporadic or random occurrence of the disease is most common (90-95%) and may not be associated with any gene mutation.  The easiest way to identify a genetic mutation causing hereditary cancer is that the family should have more than 3 to 4 members having the disease.

So even those patients who are newly diagnosed with cancer, unless there is a strong family history, need not panic into a genetic testing routinely.

3. The third group consists of those who have relatives diagnosed with breast cancer.

They have absolutely NO need for genetic testing unless there is a strong family history like group one or certain communities. Most – nearly 95% fall in this category.

I assured Sharmila, “you may have a relative just diagnosed with cancer or treated for cancer but there is absolutely no need to panic.” There is 5-10 % increase in incidence  due to family history . As you are now aware and likely to go for screening periodically, rest assured you will be SAFE.

I think Angelina Jolie has caused more anxiety than help to women.  Indeed in a sporadic mutation responsible for 95% of breast cancer, the risk is overstated and certainly does not warranty bilateral mastectomy in a young age.  In fact the risk in BRCA 2 is 29% by 50 years of age and 88% by 70 years!! BRCA1 carries a higher risk.

There is always risk in life. There is risk in life of not only relating to cancer but also to cardiac and other illnesses. Every organ can have malignancy.  Does it mean that one should sacrifice all the organs? Or worst still, have all the genes allegedly responsible for all diseases tested? Is there a simpler way of managing?

How is Angelina going to manage the risk of ovarian cancer? Her ovaries are still preserved!!

The best way is obviously a more intensive screening of those at high risk rather than putting them to genetic testing. And for all you know if only 52% of the familial cancers  had BRCA1 mutation and the rest did not have BRCA1 mutation  The presence of genetic mutations do not always manifest in “C” in every individual.  There has to be some caution but definitely don’t rush into something as traumatic as bilateral breast removal with its attendant risks and problems.

One has to realize that science is never perfect and new knowledge may be totally different from existing information.

Sharmila smiled, convinced that panic is the last reaction in fighting the Big C.

So defeat your fear and you can prevent cancer, particularly breast cancer.

She was curious to know about the genes and cancer. And I promised that I would talk on “Cancer” and “what is the role of genes”.

My take:

I personally don’t think Angelina did this as a PR exercise. It’s too traumatic and risky to undergo prophylactic bilateral mastectomy for publicity. Not for her any way. So many have undergone bilateral mastectomy and kept quiet.

But the timing should have been better to avoid a controversy on the pending legal issue on patenting BRCA1/2 genes. I do hope there was no hidden agenda. Certainly she should not promote genetic testing for all those with a relative.

Patenting genes is ridiculous. Hope U.S Supreme Court takes the right decision.

References: 

1.Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence.  D FordD F Easton, and J Peto, Am J Hum Genet. 1995 December; 57(6): 1457–1462.

2.Genetic testing for familial/hereditary breast cancer—comparison of guidelines and recommendations from the UK, France, the Netherlands and Germany D. Gadzicki & D. G Evans& H Harris et al: J Community Genet (2011) 2:53–69