Re: Risk estimate and comparison

["Bjorn Cedervall" <bcradsafers@hotmail.com>]

>>But for some cases, like with the eye tumor retinoblastoma,
>>one single event like a chromosomal break due to say an alkylation 
>> >>reaction or an ionization is enough and you get the tumor.
>
>Ok, but explain why a retinoblastoma (RB) is such a rare tumor. If repair 
>mechanisms don't work for this tumor, why isn't it very prevalent?

Retinoblastoma can be divided up into two statistical categories:

1. The one that is the result of two hits in the same cell - and not only 
that - the hits must strike the same parts of the two homologuous 
chromosomes. The probability for this is _very_ low.

2. The category that occurs due to a single event: A damaged Rb gene occurs 
with a very low frequency in the general population (this is easy to 
understand since it must always have been a killer before modern medicine 
could attempt any kind of cure) - but when an individual inherits such a 
damaged gene - all the precursor cells of the retina (part of the eye) will 
have this defect. All these cells shall divide to form the final two retinas 
which, if I recall correctly, will be composed of something like 200 million 
cells (after the age of 5-6 years, no more such cells will divide). A second 
event in _any_ of these cells (or their precursors) will cause the tumor to 
develop. This probability that a second damging event occurs is _very_ high 
(close to 100% I believe - at least 85%).
There are mechanistically several possibilities for this to occur - the 
bottom line is that the Rb function of the normal homologuous chromosome is 
lost. It can happen as a consequence of point mutation, a deletion, or loss 
of the whole chromosome (by so called non-disjunction). I guess that almost 
all children born with one Rb deficient chromosome will be identified at 
birth - simply because one of the parents have had the tumor (often in both 
eyes) and should be at least partially blind.

Please add any modifications that may make this description more complete if 
I missed any essentials,

Bjorn Cedervall   bcradsafers@hotmail.com

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