A new breast cancer gene was discovered according to a recently published article in The New England Journal of Medicine. Whereas the BrCa1 and BrCa2 genes are well known as genetic markers carrying risk for breast cancer development in young women, this is now a third gene that has been shown to confer high risk for breast cancer.
The gene is named PALB2 and loss of function mutations in this gene were shown to be the source of hereditary breast cancer. The results of the study indicated that the risk for female carriers of these PALB2 mutations to develop breast cancer was eight to nine times as high as for young women in the general population in the age group 40 years old or younger. The risk was six to eight times as high for female carriers of the mutations in the age group 40 to 60 years old as women in the general population and the risk was five times as high for women older than 60 years old. The overall breast cancer risk for women with the PALB2 mutations by the age of 70 years old was 33 percent if they did not have a family history of breast cancer and the overall risk was 58 percent if they did have a family history of breast cancer (at least two first-degree relative with breast cancer by the time they were 50 years old).
The study was carried out by a large team of scientists from many institutions and Marc Tischkowitz, from the Department of Medical Genetics at the University of Cambridge in the United Kingdom, was the lead author of the study report. In the study, risk for the development of breast cancer was determined for 362 individuals (from 154 families) with a loss of function mutation in the PALB2 gene. A modified segregation analysis, which looks for a major gene effect in pedigrees, was used to analyze risk for breast cancer development related to the PALB2 gene.
The BrCa1 and BrCa2 genes confer a higher risk for breast cancer compared to the PALB2 gene, however, the PALB2 gene risk level is not far behind. Females with one of the BrCa genes have a 45 percent to 65 percent chance to develop breast cancer by 70 years old. The overall risk for developing breast cancer in the general population is 12 percent.
The PALB2 gene has been suspected of being related to breast cancer since 2006. The recently reported study, however, has presented the evidence that makes the link solid. It has been estimated that about one in 1,000 women carry one of the PALB2 mutations. Even though the prevalence of these gene mutations is not high, the risk for developing breast cancer is high if one has the mutation.
There is some knowledge about how the three genes; that is BrCa1, BrCa2 and PLAB2, play a role in causing breast cancer. The mechanism is likely related to the repair of damaged DNA. The problem mutations in these three genes impairs the cell’s ability to repair damaged DNA and certain types of damage to DNA leaves the cell as a cancer cell, which can then divide and be the source of a cancerous tumor. Now that the PLAB2 gene has been confirmed as a new breast cancer gene, much more work will be done to better understand the role that this gene plays in contributing to breast cancer in some families.
By Margaret Lutze