Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women.
BACKGROUND
Exposure to environmental tobacco smoke (ETS) is considered to be a major lung cancer risk factor for never smokers. We investigated the hypothesis that never-smoking women who are exposed to ETS and develop lung cancer are a genetically susceptible population.


METHODS
Archival tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS (and other personal and environmental factors) and lung cancer risk. We analyzed germline polymorphisms in genes that have been associated with cancer susceptibility and whose products activate (cytochrome P450 1A1 [CYP1A1]) and detoxify (glutathione S-transferases M1 [GSTM1] and T1 [GSTT1]) chemical carcinogens found in tobacco smoke.


RESULTS
When compared with never smokers who had no ETS exposure and developed lung cancer (n = 55), never smokers with exposure to ETS who developed lung cancer (n = 51) were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) because of a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6; 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P =. 02), reaching a more than sixfold excess risk in those exposed to 55 pack-years of ETS (ETS pack-year = ETS produced by an active smoker, within a confined space such as a room, who smokes one pack of cigarettes a day for a year). No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure.


CONCLUSIONS
A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele).
Bennett
W P
WP
(Laboratory of Human Carcinogenesis, Division of Basic Sciences), National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Alavanja
M C
MC
Blomeke
B
B
Vähäkangas
K H
KH
Castrén
K
K
Welsh
J A
JA
Bowman
E D
ED
Khan
M A
MA
Flieder
D B
DB
Harris
C C
CC
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D014028:Tobacco Smoke Pollution; C413545:glutathione S-transferase T1