University of Arizona Cancer Center member Donato Romagnolo, PhD, MSc, is leading a study that suggests that external environmental and dietary factors in pregnant women may have an impact on future breast cancer risk for the offspring.
More than 40,000 Americans die from breast cancer each year. However, fewer than 10 percent of those cases involve a patient with a hereditary link through mutations in the BRCA-1 gene. Dr. Romagnolo and his team have looked into what other factors and mechanisms may contribute toward abnormal BRCA-1 behavior.
“We wanted to figure out what could possibly be responsible for the large percentage of breast cancer cases where patients have no family history of the disease, but have lower or no detectable BRCA-1,” Dr. Romagnolo said.
His team’s research suggests that various environmental and dietary conditions during pregnancy can activate the aromatic hydrocarbon receptor (AhR), which functions as a cellular sensor, leading to impaired mammary gland development in the womb. This event can, eventually, increase the offspring’s susceptibility for breast cancer — particularly if exposure to these external factors happens during key gestational development periods.
An important implication of these observations is that irregular AhR behavior during pregnancy may increase the risk of breast cancer in offspring and future generations, even for individuals with no familial history of the disease or BRCA-1 mutation carriers. The biological process through which these changes could take place is known by scientists as “epigenetics,” which can modify the risk of breast cancer without the need for alterations in the genetic code of BRCA-1 or other genes.
The findings in this study also pointed toward the potential preventative impact of dietary compounds such as resveratrol and others, which have been shown to regulate the AhR. These compounds could be useful to combat various external factors that through the AhR target the BRCA-1 gene during gestation, and reduce BRCA-1 levels in the offspring.
“Foods such as broccoli, berries, grapes, raisins, peanuts and tea contain many bioactive compounds that have protective effects towards environmental substances that work through the AhR and offer opportunities for cancer prevention,” Dr. Romagnolo said. A goal of Dr. Romagnolo’s research team is to translate these findings to the clinic with the intent of developing new markers of breast cancer risk.
Dr. Romagnolo’s findings first appeared online in the journal Molecular Carcinogenesis on Oct. 17. Co-authors on this paper include associate research professor Ornella I. Selmin, PhD, research technician Jamie L. Borg, and former Nutritional Sciences doctoral student Andreas Papoutsis.
In addition to his role at the UA Cancer Center, Dr. Romagnolo is a professor with the Department of Nutritional Sciences in the College of Agriculture and Life sciences, Director of the Mediterranean Diet and Health Study Abroad Program, the BIO5 Institute as well as an associate with the Center for Toxicology. The study was sponsored by the United States Army Medical Research and Materiel Command (grant number: DAMD 10-1-0215), the American Institute for Cancer Research (grant number: 10A058) and the UA Cancer Center Support Grant (P30CA23074).
Download PDF: Gestational Exposure to the AhR Agonist 2,3,7, 8-Tetrachlorodibenzo-p-dioxin Induces BRCA-1 Promoter Hypermethylation and Reduces BRCA-1 Expression in Mammary Tissue: Preventive Effects of Resveratrol
-Oct. 29, 2013