Half of American women have a tripled risk of lung cancer when exposed to commonly encountered levels of radon — a gas known to be the No. 1 cause of lung cancer among nonsmokers — according to results of a study from City of Hope researchers and colleagues.

An examination of women in the Midwest found that a common genetic trait raised risks of lung cancer linked to radon exposure. Researchers announced the findings June 2 at the Women Against Lung Cancer meeting in Atlanta, held in conjunction with the American Society of Clinical Oncology’s annual meeting.

“Radon is responsible for about 21,000 lung cancer deaths every year, but it’s been largely forgotten, and few homes are being tested,” said William P. Bennett, M.D., associate professor of molecular medicine at Beckman Research Institute of City of Hope, who delivered the results at the meeting. “The surgeon general issued a health warning about radon in 2005, and based on new research findings, the United States Environmental Protection Agency (EPA) now estimates that radon kills more Americans every year than do drunk-driving accidents.”

Bennett and colleagues from the National Institutes of Health and University of Iowa conducted their case-only study among 1,755 female lung cancer cases in Missouri and Iowa. They obtained tumor tissues from 270 of those cases and analyzed DNA from the samples.

The scientists also measured radon levels at the homes of the lung cancer patients. A form of ionizing radiation, radon is an odorless gas produced by the decay of naturally occurring uranium in soil and water.

Radon is a known carcinogen, and when inhaled into the lungs, it causes cancer by producing oxygen free radicals, which damage DNA. After years of exposure, some of the mutated cells become cancerous.

Researchers believe that tobacco smoke - the leading cause of lung cancer - also promotes cancer by introducing oxygen free radicals as well as scores of chemical carcinogens and trace amounts of radioactive polonium, which can damage DNA in lung tissue. Scientists know that certain enzymes in the body neutralize oxygen free radicals. One key enzyme is glutathione-S-transferase M1, or GSTM1 for short. However, about half of Caucasians (the group studied in the current report) have a genetic trait that renders them unable to make the GSTM1 enzyme.

Researchers theorized that people lacking the enzyme have higher risks of lung cancer. In a previous study, Bennett and colleagues found that nonsmoking women who lived with smokers and had the genetic trait were at twice the risk of developing lung cancer as other women. In this current study, they saw that women exposed to radon concentrations over 3.25 picocuries per liter (pCi/L) had triple the risk of lung cancer as other women.

The E.P.A. recommends that Americans consider fixing their homes if radon levels range from 2 to 4 pCi/L; the “action level” for home safety is considered 4 pCi/L. Radon-mitigation contractors use a variety of techniques to reduce radon in homes.

Although many identify radon with the eastern United States, especially Appalachia, it may be found anywhere. Areas in Ventura and Santa Barbara counties, as well as patches throughout Los Angeles County, have significant levels of radon.

Bennett notes that the team’s preliminary research shows that the elevated cancer risk may be reduced through diet. “It appears that poor vegetable intake can raise risk further, but high vegetable intake may nearly eliminate the risk,” Bennett said. “Isothiocyanates from cruciferous vegetables such as broccoli appear to be particularly helpful.

“It’s encouraging, because while radon trails only smoking as a cause of lung cancer, we can mitigate radon risks through home testing, ventilation and diet.”

Bennett co-authored a report on the findings with Matthew R. Bonner, Ph.D., M.P.H., and colleagues in the International Journal of Cancer, available online early via www.interscience.wiley.com.

For more information on radon and lung cancer risk, visit www.epa.gov/radon and www.epa.gov/radon/healthrisks.html. For information about Women Against Lung Cancer, visit http://www.womenagainstlungcancer.org/.

In addition to Bennett, Wenying Xiong, M.D., of City of Hope’s Division of Molecular Medicine, contributed to the study. Bonner, now at the State University of New York’s University at Buffalo, worked on the study while at the National Cancer Institute (NCI). Other collaborators include scientists at the University of Iowa, St. Louis University and the NCI.