How Breast Cancer Genes Work

Though we may talk of cancer as one disease, it is really many diseases wrapped up under one name. Skin cancer has little in common with pancreatic cancer and breast cancer is something else entirely.

But even breast cancers can differ. The tumor of a woman diagnosed with breast cancer at age 30 is likely very different from that of a woman whose cancer is detected when she is 65. And the causes of their cancers probably vary as well. One may derive from, say, an environmental exposure and the other from an inherited gene mutation. Even two women with the same cancer gene mutation—such as the 185delAG mutation of BRCA1 found in the Hispanic women featured in "The Secret of San Luis Valley"—may experience very different cancers, or no cancer at all.

Women who inherit a mutation in one of the two most common breast cancer genes—BRCA1 or BRCA2—have a 36 percent to 85 percent chance of developing breast cancer during their lives, and they also have a higher risk of developing ovarian and a few other cancers, according to the National Cancer Institute. (Men have an increased risk of developing breast and, possibly, prostate cancers.) By comparison, the average U.S. woman has a 13.2 percent chance of developing breast cancer. Why do these BRCA mutations increase cancer risk?

All cancers are characterized by uncontrolled cell division. These rampantly growing cells usually clump into tumors, though some cells can break free of the tumor and go on to seed more cancers elsewhere in the body (what is known as metastasis). BRCA1 and BRCA2 belong to a class of genes called tumor suppressor genes keep cell division under control. These tumor suppressor genes have many types; BRCA1 and BRCA2 work by repairing damaged DNA.

In their normal state, the BRCA genes produce proteins that piece together breaks in double-stranded DNA that can occur as the DNA is replicated during cell division. Breaks in DNA can cause mutations in other genes. (Cells also produce a host of other proteins that fix mutations caused by sources such as radiation and environmental exposures.)

Scientists have discovered hundreds of different mutations in the BRCA genes—185delAG is just one—but nearly all have the same effect of inactivating the gene. Left with only one copy of the normal gene (or none, in the case of people who inherit two copies of a BRCA gene), the cell cannot fix all the mistakes that occur, so the DNA slowly accumulates mutations. If enough of the wrong genes become mutated, cancer can develop.

According to the National Cancer Institute, Women who have a mutation in one of the BRCA genes can reduce their risk of developing cancer through prophylactic surgery—removal of the breasts, fallopian tubes or ovaries. However, the tissue left may still develop cancer, or cancer may develop in one of the other organs associated with these genes (such as the pancreas). Unfortunately, the mutations in the BRCA genes cannot be repaired.

Sarah Zielinski | | READ MORE

Sarah Zielinski is an award-winning science writer and editor. She is a contributing writer in science for Smithsonian.com and blogs at Wild Things, which appears on Science News.