According to the results of a study published in the Journal of the National Cancer Institute, a variant of the MDM2 gene known as SNP354 may increase the risk of developing breast cancer, while a variant known as SNP309 may modify the relationship between another gene (p53) and breast cancer survival.
Inherited mutations in two genes-BRCA1 and BRCA2-have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. However, since many individuals with familial breast cancer lack mutations in these genes, researchers continue to search for other inherited genetic mutations that increase the risk of breast cancer or that influence survival from breast cancer.
The p53 gene is an important tumor suppressor gene. Normal function of the gene is important for the control of cell growth. Mutations in the p53 gene that lead to loss of gene function can contribute to the development of cancer.
The MDM2 gene produces a protein that regulates p53. Some variants of the MDM2 gene may lead to reduced p53 function.
To explore the relationships among specific variants of the MDM2 gene, tumor p53 status, and risk of breast cancer, researchers conducted a study among 293 women with breast cancer and 317 women without breast cancer.
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The two variants of MDM2 that were assessed are known as SNP309 and SNP354. Among the women without cancer, 33% carried a SNP309 variant and 10% carried a SNP354 variant.
The study assessed the relationship between the MDM2 variants and risk of developing breast cancer, as well as survival with breast cancer.
- The SNP309 variant of the MDM2 gene did not influence the risk of developing breast cancer. The SNP354 variant, however, increased the risk of developing breast cancer.
- There was no link between either MDM2 variant and breast cancer survival. MDM2 status did, however, appear to influence the link between tumor p53 status and breast cancer survival. Among women without the SNP309 variant, abnormal p53 in tumor tissue resulted in worse breast cancer survival. Among women with the SNP309 variant, abnormal p53 in tumor tissue did not influence breast cancer survival.
The researchers concluded that the two MDM2 gene variants assessed in this study may play a role in breast cancer. The SNP354 variant influenced the risk of developing breast cancer, and the SNP309 variant modified the link between tumor p53 status and breast cancer survival.
Reference: Boersma BJ, Howe TM, Goodman JE et al. Association of Breast Cancer Outcome with Status of p53 and MDM2 SNP309. Journal of the National Cancer Institute. 2006;98:911-9.
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