Role of NAT2 deficiency in susceptibility to lung cancer among asbestos-exposed individuals

Our plain-English summary of Role of NAT2 deficiency in susceptibility to lung cancer among asbestos-exposed individuals, by S.T. Saarikoski, M. Reinikainen, S. Anttila, et al (Pharmacogenetics, 2000).

The study

• Authors: S.T. Saarikoski, M. Reinikainen, S. Anttila, A. Karjalainen, H. Vainio, K. Husgafvel-Pursiainen, A. Hirvonen
• Journal: Pharmacogenetics
• Published: 2000;10(2):183-5
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This short communication examined whether the NAT2 genotype, alone or combined with the GSTM1 genotype, modified susceptibility to lung cancer among asbestos-exposed individuals. The authors had earlier reported that highly asbestos-exposed workers with the NAT2 slow acetylator genotype had an increased risk of asbestosis, malignant mesothelioma or pleural plaques. The study included 205 Finnish lung cancer patients who had surgery at Helsinki University Central Hospital in 1988-97 and 294 blood donors as population controls. Patients were interviewed about smoking and work history. Their occupational asbestos exposure was classified as definite or probable (74), possible (69) or unlikely (62). Lung specimens were examined for asbestosis and subpleural fibrosis. NAT2 and GSTM1 genotypes were determined, and odds ratios were calculated by the Mantel-Haenszel method. No statistically significant associations were found between either genotype, or their combination, and lung cancer risk, and stratification by smoking or tumour type did not change this. However, eight of the 11 patients with asbestosis and all five with subpleural fibrosis had the NAT2 slow acetylator genotype (combined odds ratio 4.0; 95% confidence interval 1.2-13.2). Median lung fibre concentrations in exposed patients were 6 million and 0.6 million fibres/gram, compared with about 30 million in Finnish insulators. The authors concluded that, because exposure levels were relatively low, a role for these genotypes in asbestos-associated lung cancer could not be excluded.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This short communication reported a Finnish study comparing lung cancer patients with population controls. It asked whether two inherited differences in detoxifying enzymes, the NAT2 slow acetylator genotype and the GSTM1 null genotype (homozygous absence of the gene), affected lung cancer risk among people with differing asbestos exposure. It compared 205 lung cancer patients who had surgery at Helsinki University Central Hospital between 1988 and 1997 with 294 blood donors used as population controls. The likelihood that each patient had been exposed to asbestos at work was classified from work history as definite or probable, possible, or unlikely. The authors found no statistically significant associations between these genotypes, alone or combined, and lung cancer. However, 8 of the 11 patients who also had asbestosis and all 5 with subpleural fibrosis had the NAT2 slow genotype. Taken together, this gave an odds ratio of 4.0 (95% confidence interval 1.2 to 13.2) compared with controls, in a very small group. The authors concluded there was no significant association overall. They noted that the patients' asbestos exposure was relatively low, so a role for these genotypes could not be excluded.

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: Short communication reporting a comparison of lung cancer patients (cases) with population controls, using genotyping and Mantel-Haenszel odds ratios
• Who was studied: 205 Finnish Caucasian lung cancer patients who had surgery (pneumonectomy or lobectomy) for suspected operable lung cancer at Helsinki University Central Hospital, 1988 to 1997, and 294 blood donors used as population controls
• Exposure: Probability of occupational asbestos exposure, classified from work history as definite or probable (74 patients), possible (69) or unlikely (62); no fiber types named. The authors described the exposed patients as former construction workers. The genetic factors studied were NAT2 and GSTM1 genotypes.
• Main results:
  • NAT2 slow acetylator genotypes were slightly more frequent in lung cancer patients with unlikely asbestos exposure (57%) than in controls (52%). GSTM1 null was somewhat more frequent in patients with definite or probable exposure (53%) than in controls (47%). No statistically significant associations were observed.
  • Having both the NAT2 slow acetylator genotype and the GSTM1 null genotype did not increase asbestos-associated lung cancer risk.
  • Among the lung cancer patients, 8 of 11 with asbestosis and all 5 with subpleural fibrosis had the NAT2 slow acetylator genotype.
  • Patients with asbestosis or subpleural fibrosis combined, compared with controls, for NAT2 slow acetylator genotype: odds ratio 4.0, 95% confidence interval 1.2 to 13.2 (P value printed as 0.02; the comparison symbol is lost in the text).
  • Patients with histologically verified asbestosis or subpleural fibrosis had a median lung asbestos concentration of 9 million fibres per gram.
• The authors' conclusion: The authors concluded that they did not observe any significant association between NAT2 and GSTM1 genotypes and asbestos-associated lung cancer overall. They said a role for these genotypes could not be excluded and that more studies in differently exposed populations were needed.
• Limitations the authors state:
  • The cases had relatively low asbestos exposure, so a role for the genotypes could not be excluded.
  • The asbestosis and subpleural fibrosis finding was based on a very small subgroup.
  • The strong effect of smoking may have masked any effect of the genotypes.

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: Lung Cancer, Mesothelioma, Pleural Plaques, Occupational History, Asbestos Exposure, Fibrosis, Odds Ratio, confidence interval.

Related studies

• Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma — M. Betti, M. Neri, et al. (2009)
• Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders — A. Hirvonen, S.T. Saarikoski, et al. (1996)
• Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations — M. Neri, E. Taioli, et al. (2006)
• Genetic susceptibility to asbestos-related fibrotic pleuropulmonary changes — M.K. Kukkonen, S. Hämäläinen, et al. (2011)
• Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure — M. Neri, R. Filiberti, et al. (2005)
• Pharmacogenetically driven patient selection for a first-in-human phase I trial of batracylin in patients with advanced solid tumors and lymphomas — S. Kummar, M.E. Gutierrez, et al. (2013)

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