Lung cancer in Mexican-Americans and African-Americans is associated with the wild-type genotype of the NAD(P)H: quinone oxidoreductase polymorphism.

Age-adjusted incidence rates for lung cancer are significantly lower for Hispanics compared with non-Hispanic whites or African-Americans; differences in genetic susceptibility have been postulated as one explanation for these ethnic differences. Recently, a polymorphism of the gene encoding NAD(P)H quinone oxidoreductase (NQO1) has been described. NQO1 is a cytosolic enzyme catalyzing the two-electron reduction of quinone substrates, which is thought to be involved in both metabolic activation and detoxification of carcinogenic agents that could be involved in lung carcinogenesis. The polymorphic variant of the gene (a C-to-T transition at base pair 609) is associated with reduced NQO1 activity and resistance to anticancer agents requiring reductive activation. We studied 177 untreated lung cancer cases and 297 community controls, examining the prevalence of the NQO1 wild-type and variant alleles to assess whether the polymorphism was associated with lung cancer. Cases and controls were individuals of Mexican-American (n = 222) or African. American (n = 252) ethnicity recruited from the Houston and San Antonio areas. Overall cases were more likely to carry two copies of the wild-type NQO1 allele compared with controls (odds ratio, 1.79; P = 0.002). When cases and controls were stratified by ethnicity, the wild-type genotype was found to be approximately 2-fold more common among African-Americans (P < 0.001) than among Mexican-Americans. Multivariate analyses indicated a significant association of the wild-type genotype with lung cancer risk after controlling for the effects of age, gender, ethnicity, and smoking status (odds ratio, 1.80; 95% CI:1.09-2.97; P = 0.02). These results indicate a significant ethnic variation in the occurrence of the NQO1 base pair 609 transition and demonstrate an association of the wild-type genotype with lung cancer risk. Given the known role of NQO1 in the activation of potential lung carcinogens, the NQO1 polymorphism should be investigated further as a possible genetic risk factor for lung cancer among minority populations.

Susceptibility to lung cancer in light smokers associated with CYP1A1 polymorphisms in Mexican- and African-Americans.

The gene-environment associations between potential carcinogenic agents modified by polymorphisms in the cytochrome P450 1A1 (CYP1A1) gene and lung cancer risk were assessed in a hospital-based case-control study composed of African- and Mexican-Americans. The study involved 171 cases and 295 controls identified from the greater Houston and San Antonio metropolitan areas. Both the exon 7 and MspI polymorphisms were analyzed by RFLP of PCR-amplified DNA, and in addition, the African-American-specific polymorphism was assayed for subjects who reported that they were African-American. Logistic regression analysis was performed to assess the association between each of the CYP1A1 polymorphisms and lung cancer, adjusting for the matching variables (age, sex, ethnicity) and other potential risk factors. Interactions between pack-years smoked, CYP1A1 genotypes, and case status were also evaluated. The variant allele frequencies did not differ by case status, but the distributions of genotypes were strikingly different by ethnicity. In addition, both the exon 7 and MspI polymorphisms, but not the African-American-specific polymorphism, were modified by the amount of cigarette consumption measured in pack-years. An approximate 2-fold increase in lung cancer risk among individuals with one or more of the variant alleles was observed among light smokers (defined as having smoked < or = 30 pack-years). The respective risk ratios for the exon 7 and MspI polymorphisms were 2.26 (95% confidence interval, 0.82-6.26) and 2.03 (95% confidence interval, 1.03-4.01) at low smoking dose. No such increase in risk was found among heavy smokers (> 30 pack-years). This phenomenon at low smoking dose was also observed when the two common polymorphisms were combined, which resulted in was a progressive increase in risk with an increasing number of variant alleles. These results indicate that at low smoking levels, the MspI and exon 7 CYP1A1 genetic polymorphisms confer susceptibility to lung cancer.