Tobacco carcinogen-detoxifying enzyme UGT1A7 and its association with orolaryngeal cancer risk

Background: UDP-glucuronosyltransferase 1A7 (UGT1A7) detoxifies several tob acco carcinogens. We determined whether UGT1A7 expression is observed in no rmal orolaryngeal tissue and whether UGT1A7 allelic variations are associat ed with the risk for orolaryngeal cancer. Methods: UGT1A7 expression in nor mal orolaryngeal tissue was determined by semiquantitative reverse transcri ption-polymerase chain reaction (PCR). Buccal cell DNA isolated from 194 ca se subjects with orolaryngeal cancer and from 388 control subjects who were matched by sex, age, and race was subjected to UGT1A7 genotyping with the use of combined PCR-restriction fragment length polymorphism and allelic di scrimination analysis. All statistical tests were two-sided. Results: UGT1A 7 messenger RNA was expressed at similar levels in the esophagus, tongue, t onsil, floor of the mouth, and larynx. Genotyping revealed the presence of three variant reduced-activity UGT1A7 alleles in both Caucasians and Africa n-Americans. Individuals with any of the predicted low-activity UGT1A7 geno types had an increased risk of orolaryngeal cancer (odds ratio [OR] = 3.7; 95% confidence interval [CI] = 1.7 to 8.7) relative to subjects with the wi ld-type genotype. Both Caucasians and African-Americans with the low-activi ty genotypes had statistically significantly increased orolaryngeal cancer risk compared with Caucasians and African-Americans with the wild-type geno type (OR = 2.8 [95% CI = 1.1 to 7.6] and OR = 6.2 [95% CI = 1.2 to 31], res pectively). For subjects with the predicted low-activity genotypes, the ris ks of oral cavity cancer (OR = 4.2; 95% CI = 1.7 to 10) and laryngeal cance r (OR = 3.7; 95% CI = 0.99 to 14) were similar. There was no association be tween UGT1A7 genotype and orolaryngeal cancer risk in never smokers, wherea s subjects with predicted low-activity UGT1A7 genotypes who were light smok ers (OR = 3.7; 95% CI = 1.1 to 12) or heavy smokers (OR = 6.1; 95% CI:= 1.5 to 25) had an increased risk. Conclusions: The tissue expression of UGT1A7 is consistent with the possibility of a physiologic role in orolaryngeal c ancer. Variations in the UGT1A7 gene that reduce UGT1A7 activity may affect the risk of smoking-related orolaryngeal cancer.