October 21, 2013 – (BRONX, NY) – Gene mutations increase as people age, which helps explain why cancer usually strikes older people. But what other consequences of aging promote cancer development or protect against it?

Jan Vijg, Ph.D., Simon Spivack, M.D., M.P.H.This is one of the 24 "Provocative Questions" that the National Cancer Institute (NCI) wants researchers to address. Now, a team of scientists at Albert Einstein College of Medicine of Yeshiva University has received a $2.8 million grant from NCI to investigate this question. The researchers will examine the role of epigenetics in causing lung cancer in people of different ages.

Epigenetic changes involve chemical "tags" that turn genes on or off without affecting the genes' underlying DNA sequences. As with gene mutations, epigenetic tags accumulate with age, and their presence on genes can be influenced by environmental factors such as what you eat and the quality of the air you breathe. Scientists now recognize that aberrant epigenetic tagging plays a major role in causing many types of cancer, but just how epigenetic changes influence cancer risk still isn't well understood.

The grant award will allow Einstein researchers to focus on a vexing question related to smoking risk.

Adam Auton, D.Phil., Yousin Suh, Ph.D."Why do some smokers get lung cancer in their 40s while others who smoke their whole lives are protected until very old age?" asked Jan Vijg, Ph.D., professor and chair of genetics and the Lola and Saul Kramer Chair in Molecular Genetics at Einstein and co-principal investigator on the grant. "We will look at how a person's epigenome – the entire set of chemical tags that decorate their genes – modulates the effect of aging on lung cancer risk."

Dr. Vijg, along with co-principal investigators Simon Spivack, M.D., M.P.H., Adam Auton, D.Phil., and Yousin Suh, Ph.D., will examine lung samples from four groups of former smokers: young smokers with lung cancer, aged smokers without lung cancer, as well as young smokers without cancer and older smokers with cancer.

In studying these lung-tissue samples, the researchers will focus on an important class of epigenetic tag: the methyl groups that attach to genes. Since aging and smoking interact to determine lung-cancer risk, the researchers will determine if this interaction is influenced by the pattern of methyl groups they observe on genes as well as by the DNA sequences of the genes themselves.

"We will look at how a person's epigenome – the entire set of chemical tags that decorate their genes – modulates the effect of aging on lung cancer risk."

– Jan Vijg, Ph.D.

One goal of this work is to identify new epigenetic or genetic biomarkers that can help predict a person's risk of developing lung cancer. And since epigenetic modifications of genes are reversible, another goal is to develop ways of modifying peoples' epigenome to reduce their lung-cancer risk and perhaps delay aging as well.

Tissue samples will be provided by surgeons at Montefiore Medical Center, the University Hospital for Einstein. Dr. Spivack is professor of medicine, of epidemiology & population health and of genetics at Einstein and chief of pulmonary medicine at Einstein and Montefiore. Dr. Auton is assistant professor of genetics at Einstein. Dr. Suh is professor of genetics and of medicine at Einstein.

NCI's "Provocative Questions" is a novel funding initiative designed to ignite investigations into 24 promising but neglected or unexplored areas of research. Answering the questions would dramatically enhance ongoing efforts to prevent, treat and cure cancer.

(The grant number from NCI, part of the National Institutes of Health, is 1R01CA180126.)