Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations

Our plain-English summary of Metabolic genotypes as modulators of asbestos-related pleural malignant mesothelioma risk: a comparison of Finnish and Italian populations, by M. Neri, E. Taioli, R. Filiberti, et al (International Journal of Hygiene and Environmental Health, 2006).

The study

• Authors: M. Neri, E. Taioli, R. Filiberti, G. Paolo Ivaldi, P. Aldo Canessa, A. Verna, P. Marroni, R. Puntoni, A. Hirvonen, S. Garte
• Journal: International Journal of Hygiene and Environmental Health
• Published: 2006;209(4):393-8
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries.

In plain English

This study compared two earlier case-control studies of pleural malignant mesothelioma, one from Finland and one from Italy. It asked whether inherited variants in five metabolic genes (CYP1A1, GSTM1, GSTT1, EPHX1 and NAT2) were linked to the disease in people exposed to asbestos. The Finnish study had 48 asbestos-exposed patients and 121 construction-worker controls. The Italian analysis was limited to 57 patients with definite asbestos exposure, mainly port workers, and 255 healthy controls. New genetic tests were added to the Finnish data. CYP1A1, GSTM1 and GSTT1 on their own showed no significant link in either country. The NAT2 fast acetylator genotype was linked to higher risk in Italians (OR 1.9, 95% CI 1.0–3.4) but appeared protective in Finns (OR 0.6, 95% CI 0.3–1.2). Gene combinations also showed opposite patterns in the two countries. The authors said this difference may be due to chance in these small studies. They suggested it might also reflect the different types of asbestos used in each country.

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: Comparison and re-analysis of two previously published case-control studies (one Finnish, one Italian), updated with new genotyping for the Finnish study
• Who was studied: Finland: 48 asbestos-exposed pleural malignant mesothelioma patients enrolled 1985 to 1993 at Helsinki University Central Hospital, and 121 controls from a cohort of construction workers. Italy: 80 patients enrolled 1996 to 2003 in Genoa and Sarzana (La Spezia), reduced to 57 with definite asbestos exposure, and 255 healthy controls recruited in 1999 in the same area for a cardiovascular study
• Exposure: Asbestos exposure. Italian cases were restricted to definite exposure, mainly highly exposed workers in port or related activities. Genes studied: CYP1A1, GSTM1, GSTT1, EPHX1 and NAT2. In the discussion, citing other sources, the authors state that about 40% of asbestos used in Finland was the amphibole anthophyllite, while in Italy chrysotile was most commonly found in occupationally exposed subjects, followed by amphiboles (mainly amosite and crocidolite)
• Main results:
  • CYP1A1, GSTM1 and GSTT1 genotypes, examined separately, showed no significant association with mesothelioma in either the Italian or the Finnish study
  • NAT2 fast acetylator genotype in Italians: OR 1.9 (95% CI 1.0–3.4), a significant positive association
  • NAT2 fast acetylator genotype in Finns: OR 0.6 (95% CI 0.3–1.2), described by the authors as appearing to be a protective factor
  • EPHX1 low-activity genotype: OR 1.7 (95% CI 0.7–4.1) in Italians and OR 0.7 (95% CI 0.2–2.3) in Finns
  • In the Italian study, the EPHX1 association was stronger in a group of subjects with low asbestos exposure: OR 7.83 (95% CI 0.98–62.60)
  • Combined NAT2 fast acetylator and EPHX1 low-activity genotypes in Italians: OR 3.5 (95% CI 0.9–13.8), p for trend 0.007, described by the authors as a clear additive effect
  • The same NAT2 fast and EPHX1 low-activity combination in Finns: OR 0.6 (95% CI 0.1–2.7), p for trend 0.06
  • Combined NAT2 fast acetylator and GSTM1 null genotypes in Italians, compared with NAT2 slow and GSTM1 functional: OR 2.4 (95% CI 1.0–5.7), p for trend 0.02
  • In Finns, NAT2 fast acetylator with GSTM1 functional genotype, compared with NAT2 slow and GSTM1 null: OR 0.4 (95% CI 0.1–1.0), p for trend 0.04, described as borderline significant
  • Smoking habits did not influence the observed genotype effects (data not shown)
• The authors' conclusion: The authors concluded that the opposite results in Finland and Italy may be due to random chance, given the relatively small size of the two studies. They suggested that the different predominant forms of asbestos used in the two countries may offer an alternative or additional explanation, and called for larger studies
• Limitations the authors state:
  • The small sample size makes definitive conclusions difficult, especially for the combined genotype results
  • Actual asbestos exposure levels could not be directly compared between the two study populations
  • Italian controls were younger than the cases, which the authors state should not affect the results

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Glutathione (GSH), Asbestos Exposure.

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)
• Role of NAT2 deficiency in susceptibility to lung cancer among asbestos-exposed individuals — S.T. Saarikoski, M. Reinikainen, et al. (2000)
• Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure — M. Neri, R. Filiberti, et al. (2005)
• Asbestos exposure, manganese superoxide dismutase (MnSOD) genotype, and lung cancer risk — L.I. Wang, D. Neuberg, et al. (2004)
• Hot spot mutations in Finnish non-small cell lung cancers — S. Mäki-Nevala, V.K. Sarhadi, et al. (2016)

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