Ineffective DNA Repairs May Explain Non-genetic, Sporadic Breast Cancers

A new study has revealed that breast cancers that arise sporadically, rather than through inheritance of certain genes, likely start with defects of DNA repair mechanisms that allow environmentally triggered mutations to accumulate. The findings by researchers at the University of Pittsburgh School of Medicine, Magee-Womens Hospital of UPMC and the University of Pittsburgh Cancer Institute further indicate that potent chemotherapy drugs that target DNA in later-stage cancers could be an effective way to treat the earliest of breast tumors.

Ultraviolet light, for example, can cause mutations, but a sophisticated system of nucleotide excision repair (NER) proteins trolls the DNA strands to identify problems and initiate repair processes. The same system repairs damage caused by many environmental carcinogens, including tobacco smoke.

"Even in healthy breast tissue, this system is only about one-fifth as effective as it is in skin," said Jean J. Latimer, assistant professor of obstetrics, gynecology and reproductive sciences at Pitt's School of Medicine.

"This deficiency could set the stage for sporadic cancer development, with the risk increasing with age as DNA damage accumulates," Dr. Latimer added.

For the study, the researchers grew and assessed 19 sporadic, stage I breast tumors placed into culture directly from surgeries to test their NER pathways. In every case, there was a deficiency in repair capacity compared to disease-free breast tissue.

The findings appeared this week in the early online edition of the Proceedings of the National Academy of Sciences.

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Source-ANI