GLUTATHIONE-S-TRANSFERASE M1 AND CODON-72 P53 POLYMORPHISMS IN A NORTHWESTERN MEDITERRANEAN POPULATION AND THEIR RELATION TO LUNG-CANCER SUSCEPTIBILITY

Several polymorphic genes have been reported to be possibly involved i n modifying lung cancer risk in smokers, The gene GSTM1 is frequently deleted in human populations, and the null genotype has been reported to be a risk factor for developing lung carcinoma, A germline polymorp hism of p53 with a single-base change at codon 72 that causes an amino acid replacement of arginine (Arg; CGC) by proline (PRO; CCC) has als o been reported to be associated with cancer susceptibility in a Japan ese population, Both polymorphisms were genotyped by PCR in a northwes tern Mediterranean healthy population (n = 147) and in a group of lung cancer patients (n = 139), The results showed that the frequency of t he GSTM1 null genotype was higher in the lung cancer patients compared to the controls [odds ratio (OR), 1.57; 95% confidence interval (CI), 0.99-2.51], The histological subtypes most clearly modified were smal l cell carcinoma (OR, 1.89 CI, 0.97-3.65) and adenocarcinoma (OR, 1.93 ; CI, 0.90-4.14). The null GSTM1 genotype was more frequent among thos e cancer patients who were medium/light smokers (less than or equal to 50 pack-years) and in those who showed an onset of the disease at a m ore advanced age, The study of the p53 polymorphism in the healthy pop ulation showed allele frequencies of 0.79 (Arg) and 0.21 (Pro), The fr equencies found in the lung cancer patients were statistically similar , Both polymorphisms were studied together, and the relative risk of t he combination null GSTM1 and Pro/Pro or Arg/Pro genotypes was calcula ted taking the combination of GTSM1+ together with Arg/Arg as a baseli ne, The OR found (1.97; CI, 1.03-3.73) suggests that the Pro allele of the p53 germline polymorphism may slightly increase the risk of the G STM1 null genotype among smokers.