Understanding Hereditary Cancer

July 23, 2010
CURE, Summer 2008, Volume 7, Issue 2

Here's the state of play on some forms of cancer and their hereditary components.

Here’s the state of play on some forms of cancer and their hereditary components:

Breast Cancer

Only about 10 percent of breast cancer cases are thought to be hereditary, and of those, some proportion (estimates range from 30 to 70 percent) are accounted for by mutations in the genes BRCA1 and BRCA2. The mutations confer a big risk, raising the odds of breast cancer from about a 13 percent lifetime risk in the general population to between 50 and 85 percent. Genetic testing for mutations in BRCA1 and BRCA2 is widely available. Testing is also available for mutations in the gene TP53, which can cause Li-Fraumeni syndrome, which is very rare but raises the odds of breast and other cancers, including sarcoma, leukemia, brain tumors and adrenocortical carcinoma. Mutations in other genes, including CHEK2, have also been associated with a higher-than-average risk for breast cancer, but it’s not yet clear how or whether testing for them is useful.

Ovarian Cancer

Mutations in the same BRCA1 and BRCA2 genes are involved in ovarian cancer as well, raising the odds of ovarian cancer from less than a 2 percent lifetime risk to between 20 and 50 percent, says Karen Lu, MD, of M.D. Anderson Cancer Center in Houston. It’s thought that about 10 percent of all ovarian cancers are inherited, and that mutations in BRCA1 and BRCA2 cause most of these cases.

Colorectal Cancer

As many as 10 percent of colorectal cancer cases are suspected to have a hereditary component. The rare FAP and AFAP (see main story) are both caused by mutations in the APC gene. Mutations in other genes cause hereditary nonpolyposis colorectal cancer (HNPCC), also called Lynch syndrome, and account for about 2 to 3 percent of all colon cancers, says Lu. Lynch syndrome also raises the risk of endometrial cancer. Tests are available for both FAP and HNPCC. Mutations in another gene, MYH, are also associated with colorectal cancer, but any benefits of testing are unclear.