Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma

Our plain-English summary of Pooled analysis of NAT2 genotypes as risk factors for asbestos-related malignant mesothelioma, by M. Betti, M. Neri, D. Ferrante, et al (International Journal of Hygiene and Environmental Health, 2009).

The study

• Authors: M. Betti, M. Neri, D. Ferrante, S. Landi, A. Biava, F. Gemignani, M. Bertolotti, D. Mirabelli, M. Padoan, D. Ugolini, M. Botta, S. Bonassi, C. Magnani, I. Dianzani
• Journal: International Journal of Hygiene and Environmental Health
• Published: 2009;212(3):322-9
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is a rare and aggressive tumor of the pleura. The most important causal factor for the development of MM is occupational exposure to asbestos. Different lines of evidence suggest a role of genetic background in MM development, as for other cancers. Two published studies observed an association between MM and N-acetyl-transferase 2 (NAT2) polymorphisms. First, a Finnish study observed that the NAT2 slow acetylator phenotype was associated with an increased risk of MM. Conversely, MM risk was higher in Italian subjects carrying the NAT2 fast acetylator genotypes. The conflicting results obtained in Finland and Italy could be ascribed to random chance, considering the small panel of patients and controls in the two studies, but also ethnic or other differences may have been important. To ascertain the role of NAT2 genotype, we performed a study on 252 MM patients and 262 controls recruited in two Northern Italy areas that were characterized by high asbestos exposure, due to intense industrial activities (an asbestos cement factory in Casale Monferrato, mainly shipyards and refineries in Liguria). Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). NAT2 fast acetylator genotypes showed an increased OR, although not statistically significant, both in asbestos-exposed subjects (OR=1.47; 95% CI=0.96-2.26) and in the entire population (OR=1.38; 95% CI=0.93-2.04). These results suggest that NAT2 polymorphisms do not exert a strong effect on individual susceptibility to MM.

In plain English

This study pooled data from two case-control studies in Northern Italy. It asked whether variants of the NAT2 gene, which classify people as "fast" or "slow" acetylators, were linked to malignant mesothelioma of the pleura. It included 133 patients and 182 controls from Casale Monferrato, where an asbestos cement factory operated from 1907 to 1985. It also included 119 patients and 80 controls from the CREST biorepository in Liguria, a region with extensive shipyard activity. Results were adjusted for age and sex, and the pooled analysis also for study centre. In each area and in the pooled data, fast acetylators had higher odds ratios for mesothelioma than slow acetylators, but none of these results was statistically significant. In the pooled data the odds ratio was 1.38 (95% CI 0.93–2.04) for all subjects and 1.47 (95% CI 0.96–2.26) for asbestos-exposed subjects. The authors concluded that NAT2 genotypes do not have a strong effect on mesothelioma susceptibility. They noted that larger numbers of cases and controls might reach statistical significance, and that the mechanism for any NAT2 role is unclear.

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: Pooled analysis of two case-control studies (a population-based case-control study in Casale Monferrato and a biorepository-based case-control panel in Liguria), analysed with multivariate unconditional logistic regression adjusted for age and gender
• Who was studied: 252 patients with pleural malignant mesothelioma and 262 controls from two Northern Italian areas. Casale Monferrato: 133 cases diagnosed January 2001 to December 2005 and 182 randomly sampled local controls (blood obtained from 133 of 185 eligible cases and 182 of 418 eligible controls). Liguria (CREST biorepository): 119 patients and 80 controls (healthy subjects and patients hospitalized for non-neoplastic, non-respiratory conditions).
• Exposure: NAT2 genotypes grouped as fast versus slow acetylator, studied together with asbestos exposure. Exposure was classified as occupational (high) or domestic/environmental (low) and summarized as exposed versus non-exposed. Casale Monferrato exposure came from an asbestos cement factory active 1907 to 1985. Liguria has many asbestos-related industries, including extensive shipyard activity. Fiber types are not specified.
• Main results:
  • Casale Monferrato panel: fast acetylators compared with slow acetylators had an OR of 1.34 (95% CI 0.80–2.23) in all subjects and 1.45 (95% CI 0.86–2.44) in asbestos-exposed subjects. Neither was statistically significant.
  • Casale Monferrato, asbestos-exposed subjects: intermediate versus slow acetylators OR 1.49 (95% CI 0.86–2.60), and fast versus slow OR 1.27 (95% CI 0.47–3.38). No trend was seen, and none of the results reached statistical significance.
  • Liguria panel: fast acetylators compared with slow acetylators had an OR of 1.54 (95% CI 0.82–2.88) in all subjects and 1.66 (95% CI 0.74–3.71) in asbestos-exposed subjects. Neither was statistically significant.
  • Pooled analysis (adjusted for age, gender and study centre): fast acetylators had an OR of 1.38 (95% CI 0.93–2.04) in all subjects (134 cases and 111 controls, versus 118 cases and 151 controls among slow acetylators). Asbestos-exposed subjects had an OR of 1.47 (95% CI 0.96–2.26) (115 cases and 70 controls fast, versus 99 cases and 101 controls slow). Neither was statistically significant.
• The authors' conclusion: The authors concluded that NAT2 genotypes do not have a strong effect on mesothelioma susceptibility, and that the hypothesis of a role for NAT2 polymorphisms may require further investigation.
• Limitations the authors state:
  • The authors noted that larger numbers of cases and controls might allow the results to reach statistical significance.
  • The authors stated that the mechanism by which NAT2 could play a role in mesothelioma is unclear.
  • Participation was higher for cases than for controls, and among controls higher for younger subjects; in Liguria it also differed by sex. Analyses were adjusted for these factors.

Topics

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

Medical terms in this study, explained in our Lexicon: Meta-Analysis, Malignant Mesothelioma, Pleura, Occupational Exposure, Asbestos Exposure, Asbestos-Cement, Casale Monferrato, Odds Ratio.

Related studies

• 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)
• Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders — A. Hirvonen, S.T. Saarikoski, et al. (1996)
• Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk — L.I. Wang, D. Neuberg, et al. (2004)
• Polymorphisms in DNA repair genes as risk factors for asbestos-related malignant mesothelioma in a general population study — I. Dianzani, L. Gibello, et al. (2006)
• Role of NAT2 deficiency in susceptibility to lung cancer among asbestos-exposed individuals — S.T. Saarikoski, M. Reinikainen, et al. (2000)
• Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study — G. Matullo, S. Guarrera, et al. (2013)

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