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

Our plain-English summary of Association between asbestos exposure, cigarette smoking, myeloperoxidase (MPO) genotypes, and lung cancer risk, by M.B. Schabath, M.R. Spitz, G.L. Delclos, et al (American Journal of Industrial Medicine, 2002).

The study

• Authors: M.B. Schabath, M.R. Spitz, G.L. Delclos, G.B. Gunn, L.W. Whitehead, X. Wu
• Journal: American Journal of Industrial Medicine
• Published: 2002;42(1):29-37
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

Copyright 2002 Wiley-Liss, Inc.

In plain English

This hospital-based case-control study in Houston, Texas, compared 375 Caucasian lung cancer patients with 378 healthy controls. Participants were interviewed about smoking and work, and their blood was tested for variants of the myeloperoxidase (MPO) gene. Asbestos exposure was counted from self-report or from a longest-held job in an asbestos-related industry or occupation. Fiber type, level and duration were not known. Any asbestos exposure was linked to higher odds of lung cancer (odds ratio 1.45; 95% CI 1.04 to 2.02). The comparison group was unexposed people with the common G/G genotype. Against them, asbestos-exposed G/G carriers had an odds ratio of 1.72 (1.09 to 2.66), and exposed carriers of the A variant had 0.89 (0.56 to 1.44). Among ever smokers, the comparison group was unexposed light smokers with G/G. Heavy smokers with G/G and asbestos exposure had an odds ratio of 2.19 (1.16 to 4.11), against 1.18 (0.58 to 2.38) for A-variant carriers with the same exposures. The authors concluded that the A-allele genotypes modified lung cancer risk among people with smoking and/or asbestos histories. They noted possible recall and selection bias and limited sample size for the three-way analysis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: hospital-based case-control study (molecular epidemiology, genotyping of the MPO gene)
• Who was studied: 375 Caucasian lung cancer cases (previously untreated, histologically confirmed) from The University of Texas M.D. Anderson Cancer Center, Houston, and 378 healthy controls recruited from a managed care organization in the Houston area, frequency matched on age, sex, smoking status and ethnicity; study dates not given
• Exposure: Asbestos exposure, measured three ways and then combined into one summary variable: self-reported exposure (at least 8 hours a week for at least 1 year), longest-held employment in asbestos-related industries, and longest-held employment in asbestos-related occupations. Fiber type, level and duration were not known. Cigarette smoking (pack-years, split at the controls' mean of 45) and MPO genotype (G/G versus G/A plus A/A) were also studied.
• Main results:
  • The overall summary measure of asbestos exposure was associated with an adjusted odds ratio of 1.45 (95% CI 1.04 to 2.02) for lung cancer. 129 of 375 cases and 101 of 378 controls were classed as exposed.
  • 34.4% of cases and 26.7% of controls were classed as asbestos-exposed by the summary variable.
  • The three separate measures gave similar adjusted odds ratios. Self-reported exposure: 1.60 (1.13 to 2.27). Asbestos-related industries: 1.69 (0.95 to 3.01). Asbestos-related occupations: 1.72 (0.78 to 3.78).
  • The reference group was unexposed G/G carriers. Against them, asbestos-exposed G/G carriers had an odds ratio of 1.72 (95% CI 1.09 to 2.66), and asbestos-exposed A-allele carriers had 0.89 (95% CI 0.56 to 1.44).
  • A-allele carriers not exposed to asbestos had an odds ratio of 0.73 (0.49 to 1.06), compared with unexposed G/G carriers.
  • Among ever smokers, the reference group was G/G light smokers (under 45 pack-years) with no asbestos exposure. Against them, heavy smokers with G/G and asbestos exposure had an odds ratio of 2.19 (95% CI 1.16 to 4.11), and A-allele carriers with the same exposure profile had 1.18 (95% CI 0.58 to 2.38).
  • A similar pattern was seen when MPO genotypes were combined with pack-years smoked.
• The authors' conclusion: The authors concluded that lung cancer risks were modified by the MPO A-allele genotypes among people with histories of cigarette smoking and/or asbestos exposure. They also noted that laboratory and epidemiologic evidence for an association among MPO genotypes, asbestos and smoking was lacking.
• Limitations the authors state:
  • The study was not population-based and was not designed to examine occupational exposures.
  • Self-reported exposure information may be affected by recall bias.
  • The level of asbestos exposure, fiber type, overall duration of exposure, and whether asbestosis was present could not be determined.
  • The study population may include people only minimally exposed to asbestos.
  • Selection bias is possible.
  • The three-way analysis of genotype, asbestos and smoking had limited power and sample size.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Lung Cancer, Carcinogenesis, Occupational History, Odds Ratio.

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