DNA Damage May Increase Risk of Breast Cancer

Researchers have uncovered a pattern of DNA damage in breast connective tissues that could shed light on the early stages of breast cancer and perhaps serve as an early warning of an increased risk of cancer.

Breast cancer detection and therapy usually target epithelial cells, the primary site of breast cancers but in recent years new evidence has shown that genetic mutations that develop into cancer may initially occur in a deeper layer of the breast tissue called the stroma. Genetic changes in this connective tissue has been reported to precede the malignant conversion of tumor cells, but the actual role of stromal cells in the early stages of breast cancer initiation and progression is not well understood.

Researchers from the Pacific Northwest Research Institute (PNRI, Seattle, WA, USA) and the U.S. National Institute of Standards and Technology (NIST, Boulder, CO, USA) explored the occurrence of damage to stromal DNA caused by free radicals and other oxidants. NIST researchers used a liquid chromatography/mass spectrometry with isotope dilution to identify specific DNA lesions, while the PNRI team used Fourier transform-infrared spectroscopy to reveal subtle conformational changes to DNA base and backbone structure. Alterations such as these can change or disrupt gene expression.

The teams identified a unique oxidation-induced lesion in the DNA of breast epithelium, myoepithelium, and stroma, and found that the highest concentrations of this lesion tended to occur in women 33-46 years old, a bracket that corresponds to a known rise in the incidence of breast cancer.

In a second paper, the team studied age-related concentrations of two similar mutagenic DNA lesions and again demonstrated that their occurrence is roughly commensurate with the age at which the incidence of female breast cancer rises.

"Collectively,” they observed, "the findings suggest that lesions measured in the DNA of the stroma, which is readily obtained, may prove to be convenient and sensitive biomarkers for assessing oxidative DNA damage and for signaling an increased breast cancer risk.



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