Other Genes

Mutations (changes) in genes other than BRCA1 and BRCA2 can increase the risk of developing breast cancer. As with inheriting mutations in the BRCA genes, the amounts and types of cancer that run in families are unique to these different genes.

Inherited Cancer Syndromes and Genes Involved in Breast Cancer

There are numerous inherited cancer syndromes where susceptibility genes are passed down in families. Although these syndromes are rare, they each include breast cancer as well as many other types of cancer.

These syndromes include the following:

• Li-Fraumeni Syndrome, which is caused by mutations or changes in the P53 gene.
• Cowden's Syndrome, which is usually caused by mutations, or gene changes in the gene PTEN.
• Peutz-Jegher's Syndrome, which is usually caused by mutations, or gene changes in the gene STK11.
• ATM stands for Ataxia Telangiectasia Mutated. Carrying two mutations or changes in this gene is associated with a condition called Ataxia Telangiectasia (which can involve problems with movement and red rashes on the face and body). Individuals who carry only one mutation in this gene do not have Ataxia Telangiectasia, but they may be at an increased risk for developing cancer.
• Hereditary diffuse gastric cancer (HDGC) is a syndrome that involves inherited susceptibility to stomach and lobular breast cancer. Mutations or changes in the CDH1 gene cause about 30% of HDGC. Unfortunately, the other genes that contribute to HDGC are not known.
• Muir-Torre Syndrome is caused by mutations or changes in one of three genes: MLH1, MSH2, or MSH6. These genes are responsible for correcting mistakes that may occur when DNA is copied in normal cells. People who have Muir-Torre lack the ability to repair these minor mistakes. A buildup of these mistakes leads to increasing genetic changes within cells and eventually can lead to the cells becoming cancerous.
• P16 is another gene that may increase one's risk of getting breast cancer. Mutations or changes in this gene are associated with a condition called familial melanoma (skin cancer). The P16 gene is very important, as it controls how our DNA is replicated (copied) and how our DNA is repaired when mistakes (typos) occur in the copying process. If the P16 gene has a mutation (gene change) it does not work properly, and there is no control over DNA replication and repair. This can lead to a cancer diagnosis.

Genes that Increase Susceptibility to Breast Cancer

Recent research has identified additional genes (e.g., FGFR2) where certain variants appear to increase risk of breast cancer. While the risk-increasing forms of these genes are more common than the others mentioned in this section, their association with breast cancer is much less powerful. Someone who has these gene variants may never get breast cancer, but her risk is higher than it would be without the mutations.

There are other genes associated with an increased risk for cancer that are not yet known. This site will focus on helping patients make decisions about being tested for BRCA1 and BRCA2 mutations.