Glutathione S-transferase M1 polymorphism and the risk of lung cancer

Glutathione S-transferases (GSTs) are a family of enzymes that detoxify hydrophobic electrophiles, including polycyclic aromatic hydrocarbon carcinogens that have been implicated in the pathogenesis of lung cancer. The GSTM1 gene within the mu class of human GSTs has been shown to be polymorphic, with individuals who are homozygous for a null allele having the GSTM1-null genotype. Individuals with the GSTM1-null genotype are deficient in both the GSTM1 and GSTM3 isoenzymes in the lung. A number of epidemiological studies have been conducted to assess the association between the GSTM1-null genotype and the risk of lung cancer. Although there have been conflicting reports regarding this relationship, the current weight of evidence indicates that the GSTM1-null genotype is probably associated with a modest increase in the risk of lung cancer. This risk appears to be greater in African-American and Asian populations than in Caucasians. Recent investigations have shown that the GSTM1-null genotype combined with CYP1A1, NAT2, or GSTP1 polymorphisms confers a greater risk of lung cancer than the GSTM1-null genotype alone. Future investigations should focus on assessing the risk of lung cancer related to multiple combinations of genetic polymorphisms that may identify individuals who are at high risk for developing lung cancer with a greater degree of certainty than is currently possible. This could lead to new clinical strategies for counseling, risk reduction and the detection of lung at an early and potentially curable stage.