Gene linked to lung cancer risk in nonsmoking women
11/30/99
NEW YORK, Nov 30 (Reuters Health) -- As many as half of all nonsmoking white women are genetically more susceptible to the cancer-causing effects of environmental tobacco smoke, more than doubling their risk of lung cancer, US researchers report.
And the ``risks for women of other races and men may be similar,'' Dr. William P. Bennett, of the National Cancer Institute in Bethesda, Maryland, and colleagues write in the December 1st issue of the Journal of the National Cancer Institute.
Bennett and his team set out to determine if common genetic polymorphisms -- altered forms of a particular gene -- associated with the activation or detoxification of cancer-causing agents found in environmental tobacco smoke were associated with an increased vulnerability to lung cancer. They tested for the genetic alterations in more than 100 white women with lung cancer, none of whom had ever smoked.
The researchers identified a significant gene-environment interaction among the women, in which women with a specific genetic alteration appeared to be more than twice as susceptible to the carcinogenic effects of environmental tobacco smoke. Specifically, the alteration resulted in a deficiency in glutathione S-transferase M1, a compound known to detoxify certain carcinogens found in tobacco smoke.
Compared with nonsmoking women who reported no exposure to environmental tobacco smoke yet developed lung cancer, nonsmoking women who were exposed to environmental tobacco smoke were 2.6 times more likely to have the cancer-associated gene. Moreover, the risk of lung cancer associated with environmental tobacco smoke increased steadily and significantly with the level of exposure, reaching a more than six-fold increase in risk in women exposed to the highest levels of environmental smoke, the investigators explain.
And the genetic alteration was detected in approximately half of the women in the study, the researchers report.
``This is the first investigation to find a dose-response relationship between (environmental tobacco smoke) exposure and increasing lung cancer risk among women with a common genetic deficiency,'' Bennett and colleagues write. They calculate that the gene-environment interaction is responsible for up to one third of lung cancer cases among never-smoking women.
``Clearly, many questions remain,'' Drs. Clarice R. Weinberg and Dale P. Sandler, of the National Institutes of Health, note in an accompanying editorial. They explain that characteristics of the study suggest that the results may not be truly representative of all women with lung cancer, and note the study findings should be confirmed in additional studies.