Carcinogenesis, Vol. 21, No. 1, 49-54,
January 2000
© 2000 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
GSTM1 and NAT2 polymorphisms in operable and non-operable lung cancer patients
Environmental Medicine Unit, Department of Biosciences, Karolinska Institute, CNT/NOVUM, S-141 57 Huddinge, Sweden,
1 Department of Toxicology, National Institute of Occupational Health, PO Box 8149 Dep, 0033 Oslo,
2 Deparment of Health Care Education, Oslo College, Pilestredet 52, 0167 Oslo and
3 Department of Genetics, Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway
We have genotyped 657 Norwegian men, including 282 lung cancer patients (147 non-operable and 135 operable) and 375 healthy referents (210 smokers and 165 non-smokers), to study the possibility that glutathione S-transferase M1 (GSTM1)-null and/or N-acetyl transferase 2 (NAT2)-slow genotypes confer susceptibility towards lung cancer in smokers. Compared with smoking referents, there was a significant over-representation of the GSTM1-null genotype among patients with squamous cell carcinoma (SQ) [odds ratio (OR) = 1.7, 95% confidence interval (95%CI) = 1.1–2.7], and the NAT2-slow genotype among patients with large cell carcinoma or mixed histological diagnosis (LM) (OR = 2.5, 95%CI = 1.0–6.1). In contrast to operable patients, non-operable patients showed a clear over-representation of slow genotypes if they were younger (
63 years; versus older: OR = 3.9, 95%CI = 1.7–8.8) or younger light smokers [ 30 pack-years (PY); versus heavy smokers: OR = 5.7, 95%CI = 1.4–23.3]. Among younger light smokers, the slow genotype appeared to be associated with an increased risk of developing non-operable tumours only (OR = 6.3, 95%CI = 1.9–20.4), especially other types of tumours than SQ (OR = 10.8, 95%CI = 1.4–83.9). The null genotype (OR = 3.9, 95%CI = 1.1–13.5) and the null/slow combination (OR = 4.5, 95%CI = 1.5–13.8) seemed to increase the risk for non-operable SQ only. These results are supported by logistic regressions of patients allowing interactions between tumour type (or treatment) and PY (or age), and indicate that the GSTM1-null genotype could be an important susceptibility factor for SQ while the NAT2-slow genotype may have an impact on other types of lung cancer. Individuals with the GSTM1-null and/or NAT2-slow genotypes may constitute susceptible groups with increased risk to contract non-operable lung cancer at younger age and lower smoking dose.
Abbreviations: AD, adenocarcinoma; CI, confidence interval; GSTM1, glutathione S-transferase M1; LM, large cell carcinoma and mixed histological diagnosis; NAT2, N-acetyl transferase 2; OR, odds ratio; PAH, polycyclic aromatic hydrocarbon; PY, pack-year; SM, small cell carcinoma; SQ, squamous cell carcinoma.
4 To whom correspondence should be addressed Email: saimei.hou{at}csb.ki.se
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