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March 2001
Vol. 4, No. 3, p 15.
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Smoking, genotypes, and lung cancer
Cigarette smoking is the most common risk factor for lung cancer. The enzyme glutathione S-transferase M1 (GSTM1) is involved in detoxifying many carcinogens, including the polycyclic aromatic hydrocarbons that are found in cigarette smoke. However, many individuals lack the GSTM1 gene, that is, they have the null genotype, and they may be more cancer-susceptible than those who have the gene.

Population-based studies of the association between the null GSTM1 genotype and lung cancer have led to some contradictory conclusions. Previous studies have predominantly been conducted on Caucasian and Japanese populations. Compared with Caucasians, African Americans have a lower incidence of the GSTM1 null genotype and smoke fewer cigarettes per day, but they have a higher incidence of lung cancer. This result may indicate that African Americans are more sensitive to smoke-related carcinogens, especially if they lack the GSTM1 gene.

In a recent case-control study of more than 200 African-American patients recruited from New York hospitals, Jean G. Ford and co-workers revealed a strong association between the GSTM1 null genotype and lung cancer among heavy smokers (Carcinogenesis 2000, 21, 1971–1975). The correlation was higher for squamous cell carcinoma than for adenocarcinoma, and the risk increased with the total amount smoked over a lifetime.

These results suggest that the GSTM1 null genotype plays a role in increasing the risk of lung cancer for African-American smokers. This finding does differ from those reported in two earlier publications, which found no strong evidence of such a correlation in African Americans from California and Texas. This type of discrepancy has been encountered in studies with other ethnic groups as well.

The authors note that other genetic polymorphisms, such as variations in the cytochrome P-450 supergene family that are responsible for procarcinogen activation, may influence the association studied. Next, they will analyze the relationship between GSTM1/P-450 genotype combinations and the incidence of pulmonary malignancies. It is clear that larger-scale epidemiological and molecular–biological studies are necessary to obtain results that are more definitive.

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