It is almost certain that you or someone you know has been affected by cancer. About 20% of males and 17% of females will get cancer at some point in their lives; 13% and 9% respectively will die from it.
Why talk about cancer in a genetics course? Isn't this more properly covered in a cell biology course? Well yes, many cell biology courses spend some time talking about cancer -- but cancer is essentially a genetic disease:
Cancer is caused by random mutations
Susceptibility to cancer can be inherited, either in a Mendelian pattern or as a complex (threshold) trait
Massive changes to genome structure are one of the hallmarks of cancer
Cancer cells grow, develop, and evolve due to selective pressure
A cancer's genotype can be used to customize cancer therapy
This chapter will summarize our modern understanding of cancer through the lens of genetics: mutations, heritability, selection, and genetic testing to guide treatment.
Learning Objectives
By mastering the material in this chapter, you should be able to:
Summarize the hallmarks of cancer
Describe how cancer arises and justify the assertion that "every cancer is a unique disease."
Distinguish between tumor suppressors and (proto)oncogenes
Describe how cancer susceptibility can be inherited
Justify cancer susceptibility's classification as a complex (threshold) trait
Rationalize genetic testing to guide cancer treatment
Cancer encompasses a set of genetic diseases that lead to uncontrolled cell proliferation in multicellular organisms. The discussion of cancer also happens to be useful in a cell biology course, because it ties together many of the concepts that you just spent most of the semester learning. Although it can be caused in part by an outside agent, the development of cancer is essentially a series of uncorrected mistakes by a cell’s regular processes.
Oncogenes are generally dominant gain-of-function mutations of normal cellular genes called protooncogenes. These protooncogenes are themselves positive regulators of the cell cycle, but they are regulated by other factors, either extracellular signals or intracellular mechanisms. Mutations that turn them into oncogenes specifically remove all or some of this regulation. They thus become overactive, and try to push the cell cycle forward leading to increased proliferation.
Tumor suppressor genes normally do what would be expected from their name. Whereas the oncogenes mostly drive the cell cycle forward, the tumor suppressor genes’ primary functions are to temporarily stall the cell cycle so that DNA repair mechanisms can have time to work. However, if repair is unsuccessful after a few attempts, the tumor suppressor gene product may then trigger apoptosis rather than allow a damaged cell to replicate and potentially create another genetically damaged cell.