Calculating Penetrance

Question

For one of my homework questions it states that the penetrance for cancer amongst males is 60% and 10 males in the family inherits the allele for cancer. How many of these 10 men are expected to get cancer?

I don't need the answer specifically but I was wondering if someone could provide the steps on how to solve penetrance questions like this. Thank you.

Answer 1

Hi Siya B.,

Penetrance refers to the probability that an individual with an allele for the condition shows ANY clinical signs of the condition. So, 60% = 6 out of 10.

What's intriguing about penetrance is, since it can only refer to dominant alleles (recessive alleles never manifest, unless homozygous or unless unmasked by a different, non-dominant, allele), why isn't it 100%? There are at least two reasons: individuals are genetically diverse, and the expression of even a dominant allele is frequently affected by other portions of the individual's genome (or metabolism, I guess you would preferably say!). And, epigenetic influences -- things that turned genes on or off in the embryonic development, but didn't come from the genome specifically, such as exterior chemicals -- definitely can play a role.

Take as an analogy the individual immune system -- identical twins can develop different immune responses, based on minute differences in what they have been individually exposed to. It's very difficult to backtrack and try to determine why any complex system arrived at a final particular state.

And the consequences of ignorance can be vast! In the early days of polio vaccine, green or rhesus monkey kidney cells were used to culture the virus (Salk and early Sabin). Inadvertantly, some of the monkeys had other viral latent infections (there are dozens of such viruses known). And wouldn't you know it, one such virus, labeled SV-40, turned out to be a long-delayed retroviral carcinogenic inducer (we're talking, decades delayed). As a result, an estimated 30 million people were inoculated with polio vaccine containing SV-40, and decades later started to experience unpredictable emergence of certain nasty cancers which were previously rare enough that the increased incidence was epidemiologically evident. Worse yet, SV-40 is transmissable from adults to infants, so infection continues even to this day. (Even with that "side effect", polio vaccine was a net health benefit, polio was a terrible scourge with death or life-long disabilities.) There are many other aspects to that whole situation, which you may read up on if you wish. But the point is, that if SV-40 had had a greater penetrance (say, 30% instead of at most a few %), the health landscape would be vastly different today.

So, this "penetrance" stuff is quite an important topic, and I hope you get motivated to become your class's expert on it!

--Cheers, --Mr. d.