Common Genetic Trait Tied to Lung Cancer Risk
White women with a common genetic deficiency are at much greater risk from secondhand smoke than women without it, a research team at the National Cancer Institute has found.
In a study of 106 white female nonsmokers with lung cancer from Missouri who had been exposed to substantial amounts of secondhand smoke, the researchers found that a significantly higher than expected number of the women did not have a functioning GSTM-1 gene. This led the researchers to conclude that people with this deficiency were at a higher risk of developing lung cancer than others.
The results "indicate that [secondhand smoke] exposure may more than double the risk of lung cancer for nearly half of the white women in Western nations," the study says.
The gene being studied is one of a group involved in the creation of cancer-killing enzymes. It is missing or impaired in roughly half of all whites and Hispanics but is deficient in only about 30 percent of blacks.
"Probably the full story that will explain why particular individuals develop cancer will involve this gene plus others," said William P. Bennett, formerly of the National Cancer Institute and now with the City of Hope Cancer Center in Los Angeles. "For now, this is the effect we have identified."
Bennett said there was some evidence that the genetic trait also provides "a small additional risk" to light smokers, but little more risk to heavy smokers, whose habit is great enough to overwhelm the body's many cancer-fighting agents.
Scientists have known for some time that people exposed to secondhand smoke are at a higher risk of developing lung cancer than those who are not. The importance of the new finding, the researchers said, is that the risk was found to be much greater than expected in the white population without the GSTM-1 gene and considerably less than expected in the half with the gene.
The study analyzed the DNA collected from biopsies or surgeries of white women who had lung cancer but who never smoked. The women were also interviewed about their cancer risks, including exposure to secondhand smoke. Most of the women in the study had been routinely exposed in a confined space to at least 20 cigarettes daily for a year or more. Only white women were studied, to avoid complications resulting from differing genetic backgrounds.
The study found that the longer women with the genetic trait were exposed to secondhand smoke, the more likely they were to develop cancer.
According to Bennett, it is not unusual for certain genetic capabilities to disappear in some or all people over time. He said, for instance, that most mammals can make vitamin C from precursor molecules, and researchers believe humans once could make it as well. Now, however, they cannot. He called the widespread loss of the GSTM-1 gene a trait rather than an abnormality.
Michael Alavanja, a cancer epidemiologist with the National Cancer Institute and co-author on the study, said he opposed testing for the loss of GSMT-1 as a risk factor because "it might suggest that the individual is somehow responsible for the cancer."
"Rather than thinking of testing, I think it would be better to say that we all should be careful because half of the white population is at increased risk of developing cancer from [secondhand smoke]. We should all limit our exposure."
The study was published in this month's Journal of the National Cancer Institute. In an accompanying editorial, Clarice Weinberg of the National Institute of Environmental Health Sciences said the study was important but needed to be followed up because there was no randomized control group.
She also said the reliance on interviews with the women about whether they were ever smokers raises the possibility that some were active smokers although they said they were not. In addition, she said, the relatively small number of subjects whose DNA could be analyzed raised the possibility that the sample might not be representative of the larger population.