GSTM1 and NAT2 polymorphisms in operable and non-operable lung cancer patients.
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.
Hou
S M
SM
Environmental Medicine Unit, Department of Biosciences, Karolinska Institute, CNT/NOVUM, S-141 57 Huddinge, Sweden. saimei.hou@csb.ki.se
Ryberg
D
D
Fält
S
S
Deverill
A
A
Tefre
T
T
Børresen
A L
AL
Haugen
A
A
Lambert
B
B
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008175:Lung Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects
D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D005982:Glutathione Transferase