A Mitochondrial DNA Polymorphism is Associated with Invasive Breast Cancer in African-American Women

Robert C. Millikan, DVM, Ph.D.
University of North Carolina School of Medicine
P30ES10126 and P42ES05948

Background: Mitochondria are the "power plants" of cells and thus generate oxygen-derived free radicals during normal metabolism. Free radicals, also known as reactive oxygen species, damage DNA, both mitochondrial and nuclear, and in turn promote the development of cancer. A mitochondrial DNA polymorphism known as G10398A, which alters an important site of free radical production, has been associated with several neurodegenerative disorders. These investigators postulated that G10398A is also associated with breast cancer susceptibility.

Advance: Mitochondria from persons of African origin harbor the polymorphism much less frequently than mitochondria from Caucasian persons. In a preliminary study in African-American women, 48 with invasive breast cancer and 54 controls, these investigators found an association of G10398A with breast cancer. Women with the G10398A allele had almost three times the risk of having invasive breast cancer as those without it.

To confirm these results, a much larger study was conducted in both African-American (654 cases and 605 controls) and white women (879 cases and 760 controls). African-American women with the G10398A allele in this study had about 1½ times the risk of invasive breast cancer as those without. No association was detectable in the population of white women.

Implications: This study provides new evidence that mitochondrial genome differences may contribute to breast cancer susceptibility and may play a role in the differences in incidence of breast cancer between African-American and white women. The magnitude of the difference in risk suggests that this polymorphism is an important newly discovered risk factor to consider in the etiology of breast cancer in African-American women. The authors conclude that variations in the mitochondrial genome should not be overlooked in the search to uncover genetic factors important in breast carcinogenesis.

Citation: Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res. 2005 Sep 1;65(17):8028-33.