Heredity and Cancer

00:01 We are clearly aware that some cancers are indeed hereditary. We have just been speaking about BRCA1 and BRCA2. But what proportion of cancers really are hereditary? It’s a question to say is cancer sort of a normal process of aging or is it something that’s really, I mean, obviously it’s bad.

00:24 But is it something that we can really get rid of or no matter what, are we going to end up with cancer of something at some point because the machinery in general breaks down. Truthfully, when we look at it, the incidence of hereditary cancer, for example when we look at hereditary breast cancers with BRCA1 and BRCA2 markers, only account for 3% to 5% of breast cancer. Even if you do have those genes, it doesn’t necessitate the development of breast cancer and only 4% of colon cancers are hereditary. I think about this one. It’s really interesting when you consider our diets these days and the kinds of chemicals that a lot of people are consuming, and preservatives and such that people are consuming, and gut biota in general may be less healthy than it should be. Perhaps these sporadic mutations that arise during our life are a result more of that than they are so of an environment than they are actually heredity.

01:40 We tend to look around for an excuse of why it might have come about. But I think environment plays probably a much larger role than we think. Retinoblastoma which was for the Rb protein that I reintroduced earlier. Retinoblastoma is one of the first hereditary disorders that we had a good description of and good understanding of. It is actually probably the most hereditary form of cancer with 40% of it being hereditary versus spontaneous mutation. The bottom line is the majority, the vast, vast majority of cancers are spontaneous mutations, are not hereditary. 80% to 95%, we say are if you add together all the different possible cancers, 80% to 95% of them are sporadic.

02:44 It is about activation of oncogenes or loss of tumor suppressor genes, so mutations in either type of those genes. They can occur at any point through someone’s life. They can occur fairly randomly or as a result of environmental conditions. Also, we might see the telomeres getting clipped off.

03:10 Telomerase activity slows and the telomeres shorten and then we end up with sort of damaged sections of DNA. Usually, we think of cancer in the sense of telomerase activity being overactive but that’s after the cancer has developed. After the cancer has developed, yes, we see a renewal of telomerase activity which allows cells to divide in unregulated fashion, so not a limited number of divisions, unlimited number. If we clip off the telomeres though, we start seeing actual genetic damage further into the chromosome. So, that’s why that is there. Here’s how some of those may manifest themselves. We’ve definitely covered mutations in the coding regions of DNA.

04:00 But we could also, as we’ve seen, have them in the regulatory regions of DNA. So, affecting the promoters or the enhancers or any other regulatory proteins involved in the initiation of transcription and translation. But we can also see translocations where an interesting version of a translocation is where we see a translocation of one gene into another creating sort of like a chimeric protein which may have a novel function or it may have produced a promoter region inside the regular gene. There's translocation of a new promoter causing more uncontrolled division of that cell. Another place we can see that is in gene amplification. Let’s say we have that promoter.

05:01 It is basically turned on so that we’re promoting multiple, multiple, multiple copies of that protein.

05:13 But in addition to that, we have translocated multiple genes behind those promoters.

05:18 So, we have multiple copies of the proteins being made on multiple genes which can end up having a very excessive amount of that protein. Perhaps that protein is the gas for the car. We’ve stepped on the pedal really hard. We’re taking off with cell division, so again, uncontrolled. In short, cancer cells can exhibit multiple cytogenetic changes based on all the different regions that could be involved and the types of mutations that are common in cancer.