PT  - JOURNAL ARTICLE
AU  - Hirvonen, Ari
AU  - Pelin, Katarina
AU  - Tammilehto, Lauri
AU  - Karjalainen, Antti
AU  - Mattson, Karin
AU  - Linnainmaa, Kaija
TI  - Inherited <em>GSTM1</em> and <em>NAT2</em> Defects as Concurrent Risk Modifiers in Asbestos-related Human Malignant Mesothelioma
DP  - 1995 Jul 15
TA  - Cancer Research
PG  - 2981--2983
VI  - 55
IP  - 14
4099  - http://cancerres.aacrjournals.org/content/55/14/2981.short
4100  - http://cancerres.aacrjournals.org/content/55/14/2981.full
SO  - Cancer Res1995 Jul 15; 55
AB  - 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). ©1995 American Association for Cancer Research.