Yale Cancer Center researchers have identified a genetic biomarker that may help to determine why some people are at an increased risk of developing lung cancer.

The findings, published in the journal Cancer Research, could help identify smokers who should be carefully screened for lung cancer.

“Only 10% of smokers will develop lung cancer in their lifetime and genetic testing to determine the population of smokers who are most predisposed to develop the disease is needed to help guide better evaluation for these people,” explained Joanne B. Weidhaas, MD, PhD, assistant professor of therapeutic radiology at Yale School of Medicine and senior author on the study in collaboration with Frank Slack, PhD, associate professor in the department of molecular, cellular and developmental biology at Yale University.

"We looked for the effects of genetic variations within a human oncogene known to be affected by tiny RNA molecules, called microRNAs,” said Slack. These variations called single nucleotide polymorphisms (SNPs) predicted a significant increase in non-small cell lung cancer (NSCLC) risk in non-smokers as well as people with a moderate smoking history.

The study evaluated the prevalence of a SNP in people with lung cancer and compared this to findings in the general population. In patients with non-small cell lung cancer 20.3 percent carried the genetic alteration while 5.8 percent of the general population shared the same alteration. Based on two independent case control studies the findings show that the SNP does mark an increased risk of NSCLC.

The work breaks new ground by identifying SNPs that disrupt microRNAs and act as biomarkers of increased cancer risk. “These findings will guide us as we look for similar SNPs in all tumor-related genes,” Weidhaas said.

Other Yale University researchers included Lena Chin, Elana Ratner, Sunitha Nallur, Imran Babar, Roman-Ulrich Muller, Eva Straka, Rajeshvari Patel, Trupti Kulkarni, Robert Homer, Daniel Zelterman, and Kenneth Kidd, Yong Zu. Researchers from the Lovelace Respiratory Research Institute, Harvard School of Public Health, the University of New Mexico, and Harvard Medical School also contributed to the study.

This research was funded through a grant from the Connecticut Department of Public Health’s Biomedical Research Trust Fund and the Shannon Foundation. The National Institutes of Health provided additional support.

Citation: Cancer Research (October 15, 2008)