Beyond Genetics, Lifestyle Alters Breast Cancer Risk
Smoking, drinking, breathing polluted air, diet and exercise are all lifestyle factors that influence health – but they can also influence how our genes work. Beyond the preprogramming at birth that comes from a person’s DNA, the interaction between people and their environment can change the way genes are read and how our bodies function.
This is why researchers across the country, including Lombardi’s Peter Shields, MD, and Catalin Marian, MD, PhD, are studying the association of lifestyle and genetic variation to predict breast cancer susceptibility. One widespread lifestyle choice of particular interest to Marian is alcohol consumption.
“I think the relationship between drinking and breast cancer risk is established,” says Marian. Extensive studies worldwide have shown a connection between alcohol consumption and increased risk for breast cancer.
Normal variations in genes may inhibit or enhance the effects of alcohol consumption. For example, work by Shields, Marian and colleagues has shown that variations in the genes ADH1B and ADH1C – both of which code for enzymes critical in alcohol metabolism – may increase a postmenopausal woman’s risk for breast cancer up to two-fold if she consumes alcohol.
This is in part because, during its metabolism, alcohol breaks down into a toxic molecule that causes DNA damage. Variations in the ADH1 genes can change this process, increasing the severity of long-term damage to DNA. In this way, alcohol has the potential to disrupt many cellular pathways, and Marian says it may be one reason why increased alcohol consumption is associated with increased risk of developing breast cancer.
Another study led by Shields and Jo L. Freudenheim, PhD, of State University of New York at Buffalo, has identified another genetic variation, this time in the MTHFR gene, associated with increased breast cancer risk. By taking a detailed history of participants’ lifetime alcohol consumption, researchers were able to assess how different drinking habits affected women with the variation. Postmenopausal women who had consumed more alcohol over their lifetimes were at greater risk of developing the disease. Additionally, they found that the intensity of consumption – how much alcohol a woman chose to drink at a time – may play a role.
“There are not so many studies out there that have this information about lifestyle choices,” says Marian, “That’s the beauty of this study.”
Identifying one gene-environment interaction in one pathway only adds a small piece to the puzzle of understanding breast cancer risk. The key to understanding the whole picture in the future will be to integrate findings from multiple studies to see not just how genetic variations affect cellular pathways, but how each pathway affects the others in turn.
By Amy Dusto, Lombardi Comprehensive Cancer Center Communications