Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk

Our plain-English summary of Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk, by L.I. Wang, D. Neuberg, D.C. Christiani (Journal of Occupational and Environmental Medicine, 2004).

The study

• Authors: L.I. Wang, D. Neuberg, D.C. Christiani
• Journal: Journal of Occupational and Environmental Medicine
• Published: 2004;46(6):556-64
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To assess whether differences in genetic susceptibility to oxidative stress modify asbestos-related lung cancer risk (caused by lung inflammation, free radical production), we examined possible interactions between manganese superoxide dismutase (MnSOD) genotypes and asbestos in a hospital-based case-control study of 811 white lung cancer cases and 957 friend/spouse controls. Cumulative lifetime asbestos exposure score (AES) was calculated from self-reported duration and intensity of occupational and nonoccupational exposures. A total of 13.5% of cases and 10% of controls had "high" AES (determined by a priori cut point). The homozygous variant MnSOD genotype was associated with increased lung cancer risk among individuals with zero or "low" AES (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.52-3.01) and no association (OR = 1.00; 95% CI = 0.36-2.73) among the "high" AES group. We observed no statistically significant interaction between MnSOD genotype and asbestos exposure for lung cancer risk.

In plain English

This hospital-based case-control study in Boston asked whether a common variant of the MnSOD gene, which makes an enzyme that removes superoxide radicals, changed the link between asbestos exposure and lung cancer. Participants enrolled between December 1992 and September 2000. The gene analysis included 811 white lung cancer cases and 957 controls who were friends or non-blood-related family members. Asbestos exposure was scored from participants' own reports of job and non-job exposures, and 13.5% of cases and 10% of controls had a "high" score. After adjusting for age, sex and smoking, high exposure was linked to a lower lung cancer risk that was not statistically significant (odds ratio 0.79; 95% CI 0.56–1.11). Compared with the Ala/Ala genotype, the Val/Val genotype was linked to higher lung cancer risk among people with no or low asbestos scores (odds ratio 2.14; 95% CI 1.52–3.01) but not among those with high scores (1.00; 0.36–2.73). The authors found no statistically significant interaction between genotype and asbestos exposure. They noted that the high-exposure group was small and that heavily exposed people may have died before they could be recruited.

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 (gene–environment interaction analysis)
• Who was studied: White adults at Massachusetts General Hospital, Boston, enrolled between December 1992 and September 2000. Cases had newly diagnosed primary lung cancer. Controls were friends and non-blood-related family members of cases, or of other cardiothoracic patients. The asbestos analysis included 1950 people (966 cases, 984 controls). The MnSOD analysis included 1768 people (811 cases, 957 controls).
• Exposure: Cumulative lifetime asbestos exposure score built from self-reported occupational and environmental (nonoccupational) exposures, weighted for intensity, duration, frequency and calendar period. Scores were grouped as never, low, or high, with high defined by a predetermined cut point of a score of 10. No fiber types are named. MnSOD Ala16Val genotype was classified as Ala/Ala, Ala/Val or Val/Val.
• Main results:
  • Of the cases, 13.5% had a high asbestos exposure score, compared with 10% of the controls.
  • High vs no/low asbestos score (130 cases, 98 controls with high scores): the unadjusted odds ratio was 1.41 (95% CI 1.06–1.86). After adjustment for age, sex and smoking it was 0.79 (0.56–1.11), a reduction the authors describe as statistically nonsignificant.
  • Low vs never exposed to asbestos: the adjusted odds ratio was 1.20 (95% CI 0.92–1.55), not statistically significant.
  • Among people with no/low asbestos scores, Val/Val vs Ala/Ala gave an adjusted odds ratio of 2.14 (95% CI 1.52–3.01). Among people with high asbestos scores, it was 1.00 (95% CI 0.36–2.73). For Ala/Val, the odds ratio was 1.71 (1.27–2.31) in the no/low group and 0.88 (0.38–2.03) in the high group.
  • The test for interaction between asbestos score and MnSOD genotype was not statistically significant (likelihood ratio test P 0.20; Wald test P 0.13).
  • Among people with both the lowest asbestos and the lowest tobacco exposures, having 1 or more Val alleles was associated with a doubling of lung cancer risk (odds ratio 2.15; 95% CI 1.40–3.29). Among those with both the greatest asbestos and smoking exposures, it was associated with a reduction that was not statistically significant (odds ratio 0.81; 95% CI 0.27–2.42).
• The authors' conclusion: The authors concluded that there was no significant interaction between asbestos exposure and MnSOD genotype. In their words, at least one Val allele doubled lung cancer risk among people with no or low asbestos exposure and showed a null effect among people with high asbestos exposure. They also concluded that high asbestos exposure was associated with a nonsignificant reduction in risk after adjusting for smoking.
• Limitations the authors state:
  • The confidence intervals for the genotype estimate in the high-exposure group were wide because that group was small.
  • Possible survival bias: people with high asbestos and smoking exposure may have died before recruitment, so they may be underrepresented among cases.
  • Self-reported exposure may have been over- or underreported, causing misclassification.
  • Smoking is strongly correlated with asbestos exposure, and adjusting for it could have obscured any increased risk from asbestos.
  • Friend or spouse controls may have had asbestos exposure similar to the cases, leading to an underestimate of the asbestos effect.
  • Statistical power was limited. The study had 72% power to detect an interaction of magnitude 2.5, and smaller interactions would need larger samples.

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, Superoxide, Lung Cancer, Oxidative Stress, Inflammation, Case-Control Study, Odds Ratio, confidence interval.

Related studies

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• Manganese superoxide dismutase genotypes and asbestos-associated pulmonary disorders — A. Hirvonen, J. Tuimala, et al. (2002)
• Polymorphisms of glutathione-S-transferase M1 and manganese superoxide dismutase are associated with the risk of malignant pleural mesothelioma — S. Landi, F. Gemignani, et al. (2007)
• Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma — M. Betti, M. Neri, et al. (2009)
• Ultrastructural and chromosomal studies on manganese superoxide dismutase in malignant mesothelioma — V.L. Kinnula, T. Torkkeli, et al. (2004)
• Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma — K. Kahlos, S. Anttila, et al. (1998)

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