Association between asbestos exposure, cigarette smoking, myeloperoxidase (MPO) genotypes, and lung cancer risk.
BACKGROUND
As observed in tobacco-associated carcinogenesis, genetic factors such as the polymorphic metabolic/oxidative enzyme myeloperoxidase (MPO) could modulate individual susceptibility to asbestos-associated carcinogenesis.


METHODS
RFLP-PCR analysis identified the MPO genotypes in 375 Caucasian lung cancer cases and 378 matched controls. An epidemiological interview elicited detailed information regarding smoking history and occupational history and exposures.


RESULTS
Asbestos exposure was associated with a significantly elevated risk estimate (OR = 1.45; 95% CI 1.04-2.02). On stratified analysis, we found the MPO genotypes modified the effect of asbestos exposure on lung cancer risk. Specifically, G/G carriers who were exposed to asbestos had an odds ratio (OR) of 1.72 (95% CI; 1.09-2.66), while A-allele carriers (G/A + A/A) exposed to asbestos exhibited a reduced OR of 0.89 (95% CI; 0.56-1.44). The OR was further reduced to 0.73 (0.49-1.06) for A-allele carriers not exposed to asbestos. A similar trend was observed for the joint effects between the MPO genotypes and pack-years smoking. Next, all three risk factors (MPO genotypes, asbestos exposure, and smoking) were analyzed simultaneously for joint effects. Heavy smokers with the G/G genotype and a history of asbestos exposure demonstrated a statistically significant elevated risk estimate (OR = 2.19; 95% CI 1.16-4.11), while the A-allele carriers with the same exposure profile were at a lower risk for lung cancer (OR = 1.18; 95% CI 0.58-2.38). The A-allele genotypes demonstrated similar protective effects for the other three exposure profiles.


CONCLUSIONS
For a similar level of exposure to established carcinogens, individuals with the MPO A-allele genotypes appear to have a reduced risk of lung cancer.
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Holcombe Blvd, Houston, Texas 77303, USA.
Matthew B
MB
Schabath
Margaret R
MR
Spitz
George L
GL
Delclos
Gary B
GB
Gunn
Lawrence W
LW
Whitehead
Xifeng
X
Wu
D000368:Aged; D000483:Alleles; D001194:Asbestos / Q000009:adverse effects*; D016022:Case-Control Studies; D004198:Disease Susceptibility / Q000209:etiology; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking / Q000009:adverse effects*
D001194:Asbestos; D009195:Peroxidase