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Advances in Brief

Inherited GSTM1 and NAT2 Defects as Concurrent Risk Modifiers in Asbestos-related Human Malignant Mesothelioma

Ari Hirvonen, Katarina Pelin, Lauri Tammilehto, Antti Karjalainen, Karin Mattson and Kaija Linnainmaa
Ari Hirvonen
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Katarina Pelin
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Lauri Tammilehto
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Antti Karjalainen
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Karin Mattson
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Kaija Linnainmaa
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DOI:  Published July 1995
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Abstract

Besides asbestos exposure, the factors that determine susceptibility to malignant mesothelioma are unknown. We evaluated the risk of GSTM1 null genotype and slow acetylation-associated NAT2 genotype for malignant mesothelioma in relation to asbestos exposure. Both the GSTM1 null genotype and the NAT2 slow acetylator genotype placed individuals at about 2-fold increased risk of developing malignant mesothelioma [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.0–3.5 and OR = 2.1, 95% CI = 1.1–4.1, for the GSTM1 and NAT2 genes, respectively]. When the patients were divided into low/moderate and high exposure groups according to their asbestos exposure histories, the effect of the at-risk genotypes was mostly attributable to the high exposure groups (OR = 2.3, 95% CI = 1.0–5.6 and OR = 3.7, 95% CI = 1.3–10.2, for the GSTM1 and NAT2 genes, respectively). The individuals with combined GSTM1 and NAT2 defects had about a 4-fold risk of developing malignant mesothelioma compared to those with the GSTM1 gene and NAT2 fast acetylator genotype (OR = 3.6; 95% CI = 1.3–9.6). Moreover, the risk among subjects highly exposed to asbestos with the double at-risk genotype was more than 7-fold greater compared to those with the more beneficial genotypes of both GSTM1 and NAT2 genes (OR = 7.4; 95% CI = 1.6–34.0).

Footnotes

  • ↵1 To whom requests for reprints should be addressed, at Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland.

  • Received March 20, 1995.
  • Accepted June 2, 1995.
  • ©1995 American Association for Cancer Research.
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July 1995
Volume 55, Issue 14
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Inherited GSTM1 and NAT2 Defects as Concurrent Risk Modifiers in Asbestos-related Human Malignant Mesothelioma
Ari Hirvonen, Katarina Pelin, Lauri Tammilehto, Antti Karjalainen, Karin Mattson and Kaija Linnainmaa
Cancer Res July 15 1995 (55) (14) 2981-2983;

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Inherited GSTM1 and NAT2 Defects as Concurrent Risk Modifiers in Asbestos-related Human Malignant Mesothelioma
Ari Hirvonen, Katarina Pelin, Lauri Tammilehto, Antti Karjalainen, Karin Mattson and Kaija Linnainmaa
Cancer Res July 15 1995 (55) (14) 2981-2983;
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