Association between asbestos exposure, cigarette smoking, myeloperoxidase (MPO) genotypes, and lung cancer risk

• Published in: American journal of industrial medicine Vol. 42; no. 1; pp. 29 - 37
• Main Authors: Schabath, Matthew B., Spitz, Margaret R., Delclos, George L., Gunn, Gary B., Whitehead, Lawrence W., Wu, Xifeng
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.07.2002; Wiley-Liss
• Subjects: Aged; Alleles; asbestos; Asbestos - adverse effects; Biological and medical sciences; Case-Control Studies; Chemical and industrial products toxicology. Toxic occupational diseases; Disease Susceptibility - etiology; Female; genetic polymorphisms; Genotype; Humans; Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.); lung cancer; Lung Neoplasms - epidemiology; Lung Neoplasms - etiology; Male; Medical sciences; Middle Aged; molecular epidemiology; myeloperoxidase; Occupational Exposure - adverse effects; Peroxidase - genetics; Pneumology; Polymorphism, Genetic; Risk; Smoking - adverse effects; stratified analysis; Toxicology; Tumors of the respiratory system and mediastinum; United States; North America; Texas; America; Lung disease; Asbestos; Respiratory disease; Enzyme; Genotype; Malignant tumor; Occupational exposure; Epidemiology; Bronchopulmonary; Carcinogen; Allele; Tobacco; Peroxidases; Toxicogenetics; Predisposition; Molecular epidemiology; Bronchus disease; Genetics; Peroxidase; Oxidoreductases; Occupational history; Occupational medicine; Polymorphism
• ISSN: 0271-3586; 1097-0274
• DOI: 10.1002/ajim.10084

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. Am. J. Ind. Med. 42:29–37, 2002. © 2002 Wiley‐Liss, Inc.