Polymorphisms in CYP1A1, GSTM1, GSTT1 and lung cancer below the age of 45 years

Background. A genetic component of early-onset lung cancer has been suggested. The role of metabolic gene polymorphisms has never been studied in young lung cancer cases. Phase 1 and Phase 2 gene polymorphisms are involved in tobacco carcinogens' metabolism and therefore in lung cancer risk. Methods. The effect of metabolic gene polymorphisms on lung cancer at young ages was studied by pooling data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database. All primary lung cancer cases of both sexes who were Caucasian and ≤45 years of age at diagnosis, and the corresponding controls were selected. We obtained 261 cases and 1452 controls. Results. There was a marginally significant association between lung cancer and GSTT1 null genotype (OR = 1.2; 95% CI: 1.0-1.6), and a significant association between lung cancer and the homozygous CYP1A1 Msp1 variant allele (CYP1A1*2A and *2B) genotype (OR = 4.7 95% CI: 1.2-19.0). When data were stratified by smoking status, the association between CYP1A1 genotype and lung cancer was confined to never smokers. Conclusions. These results suggest that metabolic genetic factors play a role in lung cancer developing at young ages.