[thedoc (OP)]

Dean Cattell  asked the Naked Scientists:

   Hello naked scientists!

I've learnt that we don't understand why many people with a brca mutations remain cancer free.
Would it make sense to 'just' map the genomes of all healthy older (60 ?) women in order to be able to investigate how they are protected? If so  what kind of reseach project would be required?

Regards from Braunschweig in Germany!

PS - love the show
 
What do you think?

[evan_au]

we don't understand why many people with a brca mutations remain cancer free.

There are many steps between a genetic susceptibility to breast cancer (eg a defect in BRCA1) and actually developing cancer.

Geneticists often phrase a Yes/No genetic susceptibility as something like "Having this gene variant increases the risk of developing the disease by age Y by X%". If there is a more "analogue" measure (like height), they may say "Having this gene variant accounts for Z% of the variability". One genetic variant is rarely definitive for a condition (or it would have been discovered long ago).

BRCA1 Factors: There are many genetic variants of BRCA1, and not all of them are equally risky. You may have one faulty copy, or two faulty copies.

Factors "Upstream" of BRCA1: BRCA1 only comes into play when corrupted DNA is discovered. Environmental carcinogen exposure will differ between individuals, as will the effectiveness of the liver and other organs in breaking down carcinogens. Other signals in the DNA cause more or less production of BRCA1, which will impact the effectiveness of this protein. Other environmental factors like the age of menarche and age of first pregnancy all affect the chance of developing breast cancer.

Factors "Downstream" of BRCA1: A cancerous cell requires many mutations in order to become a lethal tumor - cell growth must become uncontrolled, they need to promote a blood supply, they need to activate telomerase and they must metastasise. A cancerous cell may never accumulate enough of these mutations before the person dies of something else. The immune system is always on the lookout for abnormal cells, and may destroy the cancerous cells; and some people may have more effective immune systems. Environmental stresses or medication can suppress the immune system.

Factors "Independent" of BRCA1: There are many paths that can produce breast cancer; a significant number of breast cancers occur in people who have normal BRCA1 genes. Some may have defects in BRCA2 or other genes.

Perhaps we understand too many reasons why there is not a direct link between BRCA1 and breast cancer.

Would it make sense to 'just' map the genomes of all healthy older (60 ?) women in order to be able to investigate how they are protected?

It is becoming cheaper to do mass genetic screening, and many teams around the world are doing just this.

But you can't just sequence the healthy people, because that won't tell you what the unhealthy gene variants are. You also need to sequence unhealthy people who develop the condition under study. Sequencing genes certainly won't tell you what the environmental influences are - these can be investigated with questionnaires.

Genetic sequencing is still so expensive that you can't discard the data after looking for just one disease - if you collect the data, it represents a valuable resource that should be mined to search for causes of other conditions.

A popular technique is for investigators to look for correlations between gene variants and incidence of disease - to either increase or decrease the incidence of disease. This can highlight genes for further study - probably some of them will be already known, and some will be new.

You need a large enough sample size for the same mutations to occur a number of times in the sample size. If you find (say) just 10 people with the same mutation, and 7 of them develop the condition, while only 20% of the general population develop the disease, that sample size is just too small to come to a firm conclusion. These 10 people will differ in many other genes.

See: https://en.wikipedia.org/wiki/100,000_Genomes_Project

[exothermic]

I've learnt that we don't understand why many people with a brca mutations remain cancer free.

Because tumor suppressor-mutations are not etiologic mediators of cancer.

[puppypower]

There are two control systems in the human body. One is connected to our genetics and the other is connected to our brain. One analogy that copies this control system is how computers are designed. As an example, say you have a computer with a poor sound card; hardware=genetics. One is not limited by this, but can enhance the sound using software. The answer is a software solution; brain.

This affect is demonstrated, all the time, during drug screening tests; placebo affect. The placebo affect is where some people will achieve an improved medical condition with a sugar pill. The power of suggestion can induce a software solution.

Theoretically, if a placebo affect can improve a condition, the power of suggestion; software induction, should also be able to cause symptoms of a disease. It may that those cured by a sugar pill, start with a placebo disease, allowing a software reversal. It may also be placebo disease, although looking the same, is prone to side affects by hardware solutions; medicines.

The way dual control system appears to work is connected to the fact that water and organics are copartners in life. You can't induce the state called life, unless both water and organics are present. Beyond that is unsubstantiated theory. Organics or water alone is inanimate matter. Together life can appear. The software solution appears to work through the water. While the hardware solution is organic based.

One can be born without a limb; gap in the genetic hardware. We can use the brain to invent a brace and prosthetic leg to compensate. This is not as good, but the software solution can fill in the hardware gap.

[RD]

... The placebo affect is where some people will achieve an improved medical condition with a sugar pill ...

Placebos do not cause an objectively measurable improvement in their medical condition, "Placebo effect" only occurs in self-assessment ...

We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003974.pub3/abstract

We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos.

http://www.nejm.org/doi/full/10.1056/NEJM200105243442106

[puppypower]

My thesis is the brain and nervous system play a role in cellular differentiation control. The question I have, for those who know more about cancer is; when cancers grow, do the original nerve connections of the root cells, divide and grow along with the cancer; like with health tissue? Or do cancer cells leave the nervous control loop?

[puppypower]

Cancer can affect nerves.  However,  the question was, do cancers develop nerve connections like healthy cells do when they multiply?

I have not been able to find the answer to this question searching the web. My guess is cancer leaves the nerve control loop. This theory would suggest that many forms of cancer propagate easier with defects in local nerve connections.

Conceptually, if we could send a signal down the nervous system, and we could read the bounce back, we could tell where there are gaps, allowing us to  identify cancer prone areas, very early. Conceptually, if we could induce nerves to grow into a cancer, this will inhibit the cancer, since it would receive control signals. Conceptually, this one technique could be used to treat a wide range of cancers; splice into the local nerve control loop for the affected cell type. If you have liver cell cancer, you spice into the nerve control loop for the liver.

The impact of the nerve control loop has more to do with ionic balance and water activity. Based on these assumptions, people with genetic disposition for a cancer, whose bodies can maintain control, can better overcome a genetic predisposition. My theory is the brain should have a backup copy of a healthy control system. It may do a system restore, periodically, to compensate. It uses a healthy point in time to reverse things before they get too out of control.