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 f or Hispanics compared with non-Hispanic whites or African-Americans; d ifferences in genetic susceptibility have been postulated as one expla nation for these ethnic differences, Recently, a polymorphism of the g ene encoding NAD(P)H quinone oxidoreductase (NQO1) has been described, NQO1 is a cytosolic enzyme catalyzing the two-electron reduction of q uinone substrates, which is thought to be involved in both metabolic a ctivation and detoxification of carcinogenic agents that could be invo lved in lung carcinogenesis, The polymorphic variant of the gene (a C- to-T transition at base pair 609) is associated with reduced NQO1 acti vity and resistance to anticancer agents requiring reductive activatio n, We studied 177 untreated lung cancer cases and 297 community contro ls, examining the prevalence of the NQO1 wild-type and variant alleles to assess whether the polymorphism was associated with lung cancer, C ases and controls were individuals of Mexican-American (n = 222) or Af rican-American (n = 252) ethnicity recruited from the Houston and San Antonio areas, Overall cases were more likely to carry two copies of t he wild-type NQO1 allele compared with controls (odds ratio, 1.79; P = 0.002), When cases and controls were stratified by ethnicity, the wil d-type genotype was found to be approximately 2-fold more common among African-Americans (P < 0.001) than among Mexican-Americans. Multivari ate analyses indicated a significant association of the wild-type geno type with lung cancer risk after controlling for the effects of age, g ender, 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 carcinogen s, the NQO1 polymorphism should be investigated further as a possible genetic risk factor for lung cancer among minority populations.