Links Between DNA Damage and Breast Cancer Studied

Aug 03, 2006

Researchers from the Pacific Northwest Research Institute (PNRI) and the National Institute of Standards and Technology (NIST) have uncovered a pattern of DNA damage in connective tissues in the human breast that could shed light on the early stages of breast cancer and possibly serve as an early warning of a heightened risk of cancer.

In the United States, breast cancer is the second leading cause of cancer-related death in women. Breast cancer detection and therapy generally target epithelial cells, the primary locus of breast cancers, but in recent years evidence has accumulated that genetic mutations that develop into cancer may occur initially in a deeper layer of breast tissue, called the stroma. Genetic changes in this connective tissue that supports the breast’s network of glands and ducts have 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.

In two recent papers*, the PNRI/NIST team explored the occurrence of damage to stromal DNA caused by free radicals and other oxidants. NIST researchers used a high-precision chemical analysis technique (liquid chromatography/mass spectrometry with isotope dilution) to identify specific DNA lesions, while the PNRI team used a spectroscopic technique (Fourier transform-infrared spectroscopy) to reveal subtle conformational changes to DNA base and backbone structures. Such alterations to the molecular structure can change or disrupt gene expression.

The team 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 in the 33- to 46-years age group, 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 observe, “the findings reveal that the structural changes in DNA described may potentially disrupt normal reciprocal interactions between the cell types, thus increasing breast cancer risk.” 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.

*Citation:

K.M. Anderson, P. Jaruga, C.R. Ramsey, N.K. Gilman, V.M. Green, S.W. Rostad, J.T. Emerman, M. Dizdaroglu and D.C. Malins. Structural Alterations in Breast Stromal and Epithelial DNA: The Influence of 8,5'-Cyclo-2-Deoxyadenosine. Cell Cycle Vol. 5, No. 11, June 1, 2006, pp. 1240-1244.

D.C. Malins, K.M. Anderson, P. Jaruga, C.R. Ramsey, N.K. Gilman, V.M. Green, S.W. Rostad, J.T. Emerman and M. Dizdaroglu. Oxidative Changes in the DNA of Stroma and Epithelium from the Female Breast: Potential Implications for Breast Cancer. Cell Cycle Vol 5, No. 15, Aug. 1, 2006, pp. 1629-1632.

Source: NIST

Explore further: Texas the front line on high school ECG debate

Related Stories

Single cells seen in unprecedented detail

Apr 27, 2015

Researchers have developed a large-scale sequencing technique called Genome and Transcriptome Sequencing (G&T-seq) that reveals, simultaneously, the unique genome sequence of a single cell and the activity ...

New target for anticancer drugs—RNA

Apr 06, 2015

Most of today's anticancer drugs target the DNA or proteins in tumor cells, but a new discovery by University of California, Berkeley, scientists unveils a whole new set of potential targets: the RNA intermediaries ...

A single-cell breakthrough

Mar 18, 2015

The human gut is a remarkable thing. Every week the intestines regenerate a new lining, sloughing off the equivalent surface area of a studio apartment and refurbishing it with new cells. For decades, researchers ...

Recommended for you

Texas the front line on high school ECG debate

4 hours ago

Cody Stephens was trying to shed some of the 290 pounds from his 6-foot-9 frame before graduating high school and attending his first college football training camp three summers ago when he took a nap and didn't wake up. ...

Middle-seat kid far from windows but closer to success

17 hours ago

Reports have been coming in about a growing-up study to explain what types of people enjoy success in adult life. The study shows that being a middle-seat child may contribute to success in later years.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.