Genetic susceptibility for lung cancer: interactions with gender and smoking history and impact on early detection policies.
OBJECTIVE
To identify a subgroup of former, current and never smokers (males and females) at high risk for developing lung cancer, based on their genetic susceptibility profiles, to estimate their lifetime probabilities of the disease, and to assess the potential mortality reduction that could be achieved by screening the high-risk group.


METHODS
Case-control data (764 cases and 677 matched controls), on two assays of DNA damage and repair (mutagen susceptibility and DNA repair capacity, DRC) in different smoking categories were used to obtain estimates of susceptibility using the formula of total probability. The estimates were inserted into a model of lung cancer natural history and detection by screening to assess mortality reduction due to screening of high-risk individuals.


RESULTS
The high-risk group was defined as that 12.5% of the population who were above the third quartile for bleomycin sensitivity and below the median for DRC. High-risk male current, former, and never smokers had lifetime probabilities for developing lung cancer of 38, 21, and 5%, respectively. Females had lower probabilities to develop lung cancer: 15, 8, and 1.5% for high-risk current, former, and never smokers, respectively. Screening of high-risk smokers (12.5% of all smokers) reduced overall mortality by 7% compared to 30% reduction if all smokers were screened. Analogous results were obtained for former and never smokers.


CONCLUSIONS
Genetic susceptibility constitutes an important factor in the selection of a high-risk group for early lung cancer detection.
Gorlova
Olga Y
OY
University of Texas M.D. Anderson Cancer Center, Houston, Tex., USA.
Amos
Christopher
C
Henschke
Claudia
C
Lei
Lei
L
Spitz
Margaret
M
Wei
Qingyi
Q
Wu
Xifeng
X
Kimmel
Marek
M
D017668:Age of Onset; D042241:Early Diagnosis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D008297:Male; D009010:Monte Carlo Method; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*