Link Between BRCA1 Gene And ATM Protein May Explain Increased Breast Cancer Risk (dateline November 11, 1999)

Scientists at the Baylor College of Medicine in Houston, Texas have discovered that the protein kinase ATM (ataxia telangiectasia) works with the BRCA1 tumor suppressor protein to repair cellular DNA damage. Though the study needs further confirmation, researchers believe that the link between the two proteins may explain why women with a defect in the ATM protein develop breast cancer more frequently than women with BRCA1 mutations alone. Women with mutated BRCA1 genes currently account for 5% of all breast cancer cases.

The new study reveals that BRCA1 may rely on the ATM protein to repair some types of cell damage. When DNA damage occurs in cells, BRCA1 helps the body repair those cells-a process that may prevent tumor development. However, BRCA1 cannot begin the process of repairing cells when the damage is caused by some types of radiation therapies . In this case, BRCA1 must rely on the ATM protein to initiate the repairs. ATM is important in recognizing when chromosomes are broken, said Dr. Elledge.

In 1994, researchers discovered that women with mutated BRCA1 or BRCA2 genes have an increased risk of developing breast and ovarian cancer . Dr. Sandhya Pruthi, MD, a Breast Health Specialist at Mayo’s breast clinic, estimates that 20% of women who carry BRCA1 mutations will develop breast cancer by age forty, 51% by age fifty, and 87% by age sixty.

Women with malfunctioning BRCA1 or BRCA2 genes also have a 20% to 60% chance of developing ovarian cancer, according to Dr. Pruthi. Additionally, BRCA1 mutations have also been linked to a higher lifetime risk of colon and prostate cancer, while BRCA2 mutations may raise lifetime risk of these and possibly other cancers.⁽¹⁾

Both men and women may inherit BRCA1 and BRCA2 gene mutations. According to the Mayo Clinic, families that typically pass on BRCA defects have the following characteristics:

• Breast cancer in two or more close relatives, such as a mother and two sisters
• Early onset of breast cancer in family members, often before age fifty
• History of breast cancer in more than one generation
• Cancer in both breasts in one or more family members
• Frequent occurrence of ovarian cancer
• Eastern and Central European (Ashkenazi) Jewish ancestry, with a family history of breast and/or ovarian cancer (researchers have identified two types of BRCA1 mutations and one BRCA2 mutation that are especially prominent in this group)

Source: Mayo Clinic HealthOasis

Women who have BRCA mutations are sometimes treated with the drug tamoxifen or chemoprevention (the use of anticancer drugs to prevent the development of breast cancer). Occasionally, surgeons may perform mastectomy on women with mutated BRCA genes, although many health care professionals favor less invasive measures.

Additional Resources and References:

• (1) The Mayo Clinic’s HealthOasis offers information on BRCA gene mutations at http://www.mayohealth.org/mayo/9910/htm/brca.asp.
• For additional information on risk factors for breast cancer, please visit http://www.imaginis.com/breasthealth/bc_risks.asp.
• The November 4 Reuters Health report, "Link between protein may explain breast cancer risk," is available online at http://www.reutershealth.com/cgibin/o/eline.viewdoc?file=/opt/netscape/Suitespot/
  docs/news/eline/open/199911/1999110408.meta .