THE GSTM1 NULL GENOTYPE AS A POTENTIAL RISK MODIFIER FOR SQUAMOUS-CELL CARCINOMA OF THE LUNG

The identification of genetic traits that predispose individuals to en vironmentally induced cancers is one of the challenges in the assessme nt of individual cancer risk. For this reason, individual variations i n the expression of enzymes involved in biotransformation reactions ha ve been extensively studied. One such polymorphic enzyme is GSTM1, whi ch belongs to the class Mu of glutathione S-transferases (GSTs), and i s only expressed in 55-60% of Caucasians. Previous data suggest that s mokers lacking GSTM1 activity may be at greater risk of developing lun g cancer. In this study, we used a polymerase chain reaction-based met hod to examine this issue in a Finnish study population. We found that 44% of a control group of 142 individuals lacked the GSTM1 gene, i.e. they had the GSTM1 null genotype; the rest were either homozygous or heterozygous for the expressed GSTM1 alleles. In a group of 36 patient s with non-neoplastic pulmonary diseases, an identical distribution wa s observed. However, among 138 lung cancer patients the distribution o f the GSTM1 genotypes deviated from that found in the healthy controls (53% nulled; odds ratio 1.5, 95% confidence interval 0.9-2.3). Furthe rmore, when the lung cancer patients were analysed by tumour type, a s tatistically significant increase in the GSTM1 null genotypes (62%; n = 71) was seen in the squamous cell carcinoma group, with an odds rati o of 2.1 (95% confidence interval 1.2-3.8). These data support the sug gestion that GSTM1 null genotype may act as a risk modifier in lung ca ncer.