CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people

Abstract

CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(2) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(2). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR ¼ 6.28; m2/GSTM1(2), OR ¼ 3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/ C, OR ¼ 1.39; m2/c2, OR ¼ 2.00; val/C, OR ¼ 1.45; val/c2, OR ¼ 0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(2), 7.38 for m2/val and 3.68 for m2/GSTM1(2), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons.