Now in today’s NY Times
there is an article by some woman who is concerned about here genes. As the
writer states:
I jogged into the Stanford Cancer Clinic with my
boyfriend, the youngest people there by two decades. We stood there sweating
and holding hands, a jarring sight in the sickly light.
“You are 18, right?” the receptionist asked. Behind me, a
woman so gaunt that her cheekbones protruded rolled by in a wheelchair. The
oncologist called me alone to the exam room, and I told her the story I had
revealed to more doctors than friends: I carry the BRCA1 mutation, which gives
you a 98 percent chance of developing cancer.
Somatic versus germline, this is somatic. Namely the
presence of this gene mutation in a Bayesian sense yields a high probability of
incidence. So what does one do? Remove the offending organs, watch and wait,
forget about it? All of these are options, and options that have costs and
consequences. Remember the aphorism, “prior planning prevents poor performance”.
Now what can one do when one may be faced with such a dilemma?
Let us consider several examples. They may all be primarily somatic and they
are all Bayesian. There are two questions; what to do when and why to do what?
Let us consider the first question; what to do when?
1. Colon Cancer: Assume there are three family members who
have had colon cancer, two first degree, mother and sister, and a second
degree, an aunt. What should one do? This tells one almost as much as BRCA
status. Clearly if one has this family history one should have frequent colonoscopies.
Finding an adenoma early means it is excised before becoming malignant. It
reduces the risk of a malignancy.
2. Melanoma: Assume that one has two first degree relatives
with melanoma and that you have had four atypical or dysplastic nevi. Now what
should one do? Clearly one has a significantly elevated risk of melanoma.
Melanoma for the most part is on the surface skin, it can also be in the eye,
colon, mouth, or other epithelium. So how best to handle it? Periodic skin
examination and excision of lesions as early as possible, seems at present to
be the best. Are there any gene tests? Not really, not yet. But one must
euphemistically just keep ahead of the bow wave.
3. Prostate Cancer: This gets tricky and political. Assume
you have one first degree relative who dies of a highly aggressive form of
prostate cancer; PSA of 4-40 in two years and 40-dead in another two. You have
annual PSA tests, best we can do, excluding PCA3, and you find a velocity of
0.8 pa. Namely there is a sudden spike. What to do? Here is where its gets
political. Akin to the BRCA issue, kind of, you get a prostate biopsy. It is
negative. Does that tell you something? Yes but not all, a second one in 912
months is essential, especially if PSA still rising. What you see is a complex
process, with risks, costs, and uncertain outcomes.
4. BRCA Breast Cancer Presence: Now look at the case in the
paper. You have relatives with BRCA mutation positive and you wonder what to
do. Now that depends. In this case your test if also showing a mutation means
you have a very elevated risk of breast and ovarian cancer. Do you get a
mastectomy and the ovaries removed? It is costly and yet the risk if
substantial. It is disfiguring and possibly even more. Is the cost worth it, is
the discomfort, physical and mental worth it, possibly. It is a personal
decision. For society is it worth it, yes, having a productive member may very
well be more important than having a deceased one.
Now the author continues:
So was I wrong to unwind my double helix?
My risks of getting cancer at 21 are too low for me to do
anything differently to better my odds. The knowledge is both irrelevant and
painful; it’s obsessed me and made me behave irrationally. I wake from nightmares
in which I am dying from cancer. I reread the memoirs of patients with
metastatic disease until I can’t see the text through my tears. In my
supposedly rational pursuit of knowledge, I’ve gone a little mad.
Despite an excess of information, I pursued more,
enrolling in Stanford’s cancer biology class. The professor filled his slides
with dark oncological puns, lecturing with the almost robotic detachment I
sometimes see in those who work closely with cancer. Maybe I, too, am becoming
robotic. I can laugh at the puns, calmly press lecturers on survival rates for breast
cancer, marvel at the elegant molecular mechanisms by which it eats us alive.
Just as tumors eventually swell too large for their hosts to endure, will all
this knowledge grow past what I can handle?
Now let us consider the second question, why to do what?
This is the tough question. This is the self-searching, soul searching,
process. Each person in a way answers it differently. I have seen the following
types of people:
1. Pragmatics: These people just do not want to leave a mess
around, and they believe that if they get ill they create a mess for themselves
and others and then why not just take preventive measures now and get the risk
reduced if possible. The go for colonoscopies, skin exams, and yes eve gene
testing, if the result has a positive mitigating factor. If the gene test,
however, shows a deadly disease potential for which there is no cure, then let
fate take its toll. On a cost benefit analysis basis these are not the cheapest
overall for society, but are cheap.
2. Hypochondriacs: Yes they exists, they want every test no
matter how costly and how ineffective. On a cost benefit basis, this cost a
fortune.
3. Deniers: These people would not get tested for any reason
until the end is near. The old man who has not had a bowel movement for eight
weeks, has lost 20% body weight and has sever back pain. They he finally is
dragged in and we see metastasized pancreatic cancer, and he has a best a week
to live. On the cost basis, they are the lowest. In this case they go from
diagnosis to a hospice for a very short while.
4. The Terrified: This is a mix between the hypochondriac
and the denier. They have a real basis for concern, yet they do not outright
deny it. They vacillate between considering and effecting preventive care and
then falling back into nothing for fear of the result.
These four groups are just a few of the generalizations that
one sees. But one of the most important questions that a physician can ask
themselves is what type of patient am I seeing, how will they react, what
motivates them to do the right thing, assuming we know what that even is. Thus
how does a physician motivate a smoker to stop, a diabetic, Type 2, to shed
weight, and a drug abuser to quit? What of the mammogram for a woman, do we
harass her to have one? Evan if there is no family history. All too often we
have the one test fits all, yet with genomic tests we do have much better
tools. How will a patient react?
In ten years of less, along with the CBC, done by a simple
machine, we will have a full gene profile of somatic genes. What do we do with
it? Knowledge will change each year as we understand more and more. Yet the
full gene profile may not change. What does the patient want to know, need to
know, and what does the patient not really have to know? These will be the
driving questions.
But in a way this article is akin to the first and second
year Med students, who often come down with diseases they are studying, at
least a few come down with certainty with Dengue Fever, despite the fact that
they never left Massachusetts. Then it slowly disappears. The more one knows
the more one understands the disease and the person often separate, but always
in the same package.
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