RT Journal Article
SR Electronic
T1 Inherited <em>GSTM1</em> and <em>NAT2</em> Defects as Concurrent Risk Modifiers in Asbestos-related Human Malignant Mesothelioma
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 2981
OP 2983
VO 55
IS 14
A1 Hirvonen, Ari
A1 Pelin, Katarina
A1 Tammilehto, Lauri
A1 Karjalainen, Antti
A1 Mattson, Karin
A1 Linnainmaa, Kaija
YR 1995
UL http://cancerres.aacrjournals.org/content/55/14/2981.abstract
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.