Glutathione S-transferase M1 (GSTM1) can detoxify many carcinogens, includi
ng polycyclic aromatic hydrocarbons such as those from cigarette smoke. Tho
ugh a number of studies have been published about the association between G
STM1 polymorphism and lung cancer, this association has received limited at
tention in the African-American population. We conducted a case-control stu
dy to investigate the role of GSTM1 polymorphism in the development of lung
cancer in African-Americans. Specimens of DNA from 117 lung cancer cases a
nd 120 controls were assayed for detection of GSTM1 genotype by polymerase
chain reaction (PCR), The odds ratios (ORs) and 95% confidence intervals (C
Is) for lung cancer associated with homozygous deletion of the GSTM1 gene a
nd other risk factors were estimated by logistic regression. Thirty-seven o
f the 117 cases (31.6%) and 24 of the 120 controls (20.0%) had the GSTM1 nu
ll genotype; the OR was 2.10 (95% CI 1.07-4.11) after adjustment for age, g
ender and smoking. The association was higher for squamous cell carcinoma (
OR 2.98, 95% CI 1.09-8.19) than for adenocarccnonma (OR 1.95, 95% CI 0.81-4
.66). We observed a stronger association between GSTM1 null genotype and lu
ng cancer among heavy smokers with greater than or equal to 30 pack-years (
OR 4.35, 95% CI 1.16-16.23). This association was also found in squamous ce
ll carcinoma (OR 6.26, 95% CI 1.31-29.91), In the analysis combining GSTM1
polymorphism and smoking, smokers with the null genotype had high risk (OR
8.19, 95% CI 2.35-28.62) compared with non-smokers with the wild-type genot
ype, and the risk increased with smoking cigarette pack-years (P = 0.0001 f
or trend). Our results suggest that GSTM1 polymorphism plays a role in the
development of lung cancer and modifies the risk for smoking-related lung c
ancer in African-Americans.