Researchers have identified an inherited abnormal gene that can lead to a high susceptibility for breast cancer, a discovery that helps explain why a tendency to develop certain malignant tumors sometimes runs in families.
In a study in today's issue of the journal Science, a group of scientists say the cancer-promoting mutation was found by genetic studies of a group of families that have an exceptionally high rate of six types of cancers, including breast cancer.
"Up until now there have been no inherited genes isolated and identified which provided susceptibilities to some of the common adult malignancies," said Stephen Friend, a Massachusetts General Hospital Cancer Center scientist.
Friend, the lead author of the study, said the mutation was found on what is called the p53 cancer suppressor gene. For people who inherit a mutated p53 gene, he said, "their chance of getting a malignancy by age 60 is 90 percent."
Andrew Feinberg, a University of Michigan Cancer Center researcher and co-discoverer of genes related to a rare kidney cancer, said the p53 discovery adds a step in the cascade of cell changes that is thought to lead to some cancers.
"From a scientific viewpoint, it is very important because it helps us understand the sequence of events that lead to cancer," said Feinberg. He emphasized that there are other steps, still unknown, that cause a normal cell to become cancerous.
The p53 gene is one of a group of genes that control cell growth. The gene, in effect, blocks the uncontrolled division of cells. If this function is lost through mutation, then the cell lacks one of the controls that keep division in balance.
The mutated p53 gene has been detected in a number of types of cancers, but the new study is the first to find the mutation can be inherited.
Friend said he and his colleagues isolated the specific p53 gene mutation by studying people with what is called the Li-Fraumeni syndrome. These are families in which there is an inherited tendency to develop one of six types of cancer at an early age, often during childhood.
Breast cancer is the most common malignancy among Li-Fraumeni families, but they can also develop leukemias, brain tumors, sarcomas of the bone and cancer of the adrenal gland.
The researchers discovered the mutation in the cells of Li-Fraumeni family members who had cancer, but not in those family members who were free of the disease.
Friend said that in the affected family members the p53 mutation was found in every cell, indicating it was passed genetically from one generation to another.
Although the mutated gene is closely related to an inherited tendency for breast cancer, Friend said a malfunctioning p53 gene is not the only genetic cause of breast cancer.