Genetic Contributions to Cancer

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Genetic Contributions to Cancer

Germline mutations in tumor suppressor genes are often seen in hereditary forms of cancers. The progeny of a sex cell with a mutated tumor suppressor gene will be born with one “bad” copy of the gene. During their lifetime they will encounter normal mutations from carcinogens and replication errors. If another mutation happens to occur in the only “good” copy of the tumor suppressor gene that the person has left, they will have a much higher chance of getting cancer. Because the original mutation that they carried is in every cell in their body including their sex cells, they are likely to pass the bad copy down to their progeny as well and therefore the increased risk of cancer is also passed down. This is what occurs in familial forms of cancer. These cancers typically occur at a younger age than non-genetic forms of cancer because the person only needed one more hit to deactivate the gene.
Not all mutations are created equal. A mutation in some genes can have no detrimental effect, whereas other mutations can have drastic effects. Remember we have redundancy built into our genome; we have one copy of every gene from our mother and one copy from our father. It is hypothesized that for cancer to form both copies of the gene must be mutated, called the two-hit hypothesis. This is why many cancers don’t occur until later in life, it takes a long time to accidentally and randomly mutate both copies the same gene. However, people born with one “bad” copy of a gene only have one more hit before the gene is completely deactivated.
Image courtesy of Wikimedia

Two hit malignant transformation with chromosome loss