By Stephen Ornes

Cracking Cancer’s Code

Genetics is key to unlocking cancer’s causes

By Stephen Ornes

In a 2008 meta-study from the Journal of the American Medical Association, researchers from the Fred Hutchinson Cancer Research Center in Seattle looked at more than 300 genome-wide studies and found that only about one-third of the genetic variations identified by them were likely to be linked to cancer.

Cancer Culprits
Even though no single cancer is caused by a single genetic variation, a single variation may play a role in the formation of many cancers. For instance, in the same August issue of Nature Genetics in which Bondy and her team reported on a GWAS for glioma, she and four other research groups independently fingered the same region of the same chromosome while looking for genetic culprits in four different types of cancer.

In other words, even though each type of cancer may not be caused by a single gene, a single gene may play an important role in the development of many types of cancer. The reason for this, says Bondy, may be that the genetic variation is involved in some chemical activity common to different types of tumors.

In addition to linking specific parts of the genome to cancer, the field of cancer genetics may turn up other ways to improve human health. Last October, when the Cancer Genome Atlas linked three problem areas in the genome to glioblastoma, researchers also learned why some cancer treatment may, ironically, contribute to the formation of new cancers. Chemotherapy drugs work by crippling the DNA of the cells they encounter, and doctors and survivors hope that the drugs kill tumor cells, not healthy cells. Cancer Genome Atlas researchers found that temozolomide (Temodar), a drug used to treat glioblastoma, may also cause mutations in genes that would normally repair damaged DNA. With their repair genes disabled, cells are more susceptible to mutations, and as a result, patients treated with temozolomide are more likely to face a cancer recurrence. This finding may not be good news for patients who have been treated with temozolomide, but it could help to improve treatment for patients in the future.

The evolution of the field of cancer genetics has been a process of asking questions which, in turn, lead to deeper questions—and to apparent paradoxes at the molecular level. No cancer is caused by a single genetic mutation, for example, but a single mutation may play a role in many different kinds of cancer. Only a small fraction of cancer can be blamed on specific inherited genetic mutations, but all cancer at some level is inherited—since people inherit the ability to repair DNA damage.

Even though the path ahead toward successful cancer treatment often appears steep and challenging, the scientific understanding of cancer’s cause has come a long way since the Victorians blamed sadness. Recent research has turned up some landmarks of hope, like targeted therapies that work against specific genetic mutations, along with effective screening tests that can alert a healthy person to increased risk. If the road seems longer now than it ever has before, it’s only that we have a better idea of what it looks like.