GENETIC SUSCEPTIBILITY TO LUNG-CANCER WITH SPECIAL EMPHASIS ON CYP1A1AND GSTM1 - A STUDY ON HOST FACTORS IN RELATION TO AGE AT ONSET, GENDER AND HISTOLOGICAL CANCER TYPES

Genetically based differences in metabolism, related to MspI restricti on site and Ile-Val polymorphisms of the cytochrome P450 (CYP) 1A1 gen e and the null genotype of glutathione transferase class mu (GSTM1), h ave been reported to be associated with lung cancer susceptibility. Th e present study was set up to establish the frequencies of the polymor phic genotypes of CYP1A1 and GSTM1 in Sweden, to evaluate a possible i ncreased incidence of the genotypes associated with higher lung cancer risks among Swedish lung cancer patients and to try to make a combine d risk estimate for carriers of multiple risk alleles. In a healthy co ntrol group, all under 66 years of age, 53% (174/329) of the subjects were of the GSTM1(-) genotype, while in a hospital control group 49% ( 39/79) carried the GSTM1(-) genotype. In the investigated lung cancer patients this genotype was found in 56% (165/296) and among those pati ents diagnosed before 66 years of age the deficient genotype was found in 60% (78/131). The highest proportion of the GSTM1(-) genotype was found in patients diagnosed with adenocarcinoma (63%, 29/46) and small cell carcinoma (72%, 21/29) before 66 years of age and among female s quamous cell carcinoma patients (79%, 15/19). The allelic variants in CYP1A1 were equally distributed in lung cancer patients and controls. The m1/m2 and m2/m2 genotypes of the MspI site and the Ile/Val genotyp e were, however, slightly over-represented in squamous cell carcinoma patients. Among patients with squamous cell carcinoma diagnosed before 66 years of age the m1/m2 genotype was found in 28% (10/36), whereas the same genotype was observed in 16% (52/329) of healthy control subj ects. A combined risk of squamous cell carcinoma was indicated for pat ients, diagnosed before 66 years of age, carrying both GSTM1(-) and m2 alleles (OR = 3.0, 95% CI = 1.2-7.2).