Tobacco carcinogen-detoxifying enzyme UGT1A7 and its association with orolaryngeal cancer risk.
BACKGROUND
UDP-glucuronosyltransferase 1A7 (UGT1A7) detoxifies several tobacco carcinogens. We determined whether UGT1A7 expression is observed in normal orolaryngeal tissue and whether UGT1A7 allelic variations are associated with the risk for orolaryngeal cancer.


METHODS
UGT1A7 expression in normal orolaryngeal tissue was determined by semiquantitative reverse transcription-polymerase chain reaction (PCR). Buccal cell DNA isolated from 194 case 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 discrimination analysis. All statistical tests were two-sided.


RESULTS
UGT1A7 messenger RNA was expressed at similar levels in the esophagus, tongue, tonsil, floor of the mouth, and larynx. Genotyping revealed the presence of three variant reduced-activity UGT1A7 alleles in both Caucasians and African-Americans. Individuals with any of the predicted low-activity UGT1A7 genotypes 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 wild-type genotype. Both Caucasians and African-Americans with the low-activity genotypes had statistically significantly increased orolaryngeal cancer risk compared with Caucasians and African-Americans with the wild-type genotype (OR = 2.8 [95% CI = 1.1 to 7.6] and OR = 6.2 [95% CI = 1.2 to 31], respectively). For subjects with the predicted low-activity genotypes, the risks of oral cavity cancer (OR = 4.2; 95% CI = 1.7 to 10) and laryngeal cancer (OR = 3.7; 95% CI = 0.99 to 14) were similar. There was no association between UGT1A7 genotype and orolaryngeal cancer risk in never smokers, whereas subjects with predicted low-activity UGT1A7 genotypes who were light smokers (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 cancer. Variations in the UGT1A7 gene that reduce UGT1A7 activity may affect the risk of smoking-related orolaryngeal cancer.
Zheng
Z
Z
Division of Cancer Control, H. Lee Moffitt Cancer Center and Research Institute, Interdisciplinary Oncology Program and Department of Biochemistry, University of South Florida, Tampa 33612, USA.
Park
J Y
JY
Guillemette
C
C
Schantz
S P
SP
Lazarus
P
P
D000483:Alleles; D019943:Amino Acid Substitution; D044383:Black People / Q000235:genetics; D002273:Carcinogens / Q000493:pharmacokinetics*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D003062:Codon; D015331:Cohort Studies; D004947:Esophagus / Q000201:enzymology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D007830:Larynx / Q000201:enzymology; D008019:Life Style; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000201:enzymology; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D009518:New York / Q000453:epidemiology; D009928:Organ Specificity; D014066:Palatine Tonsil / Q000201:enzymology; D015143:Philadelphia / Q000453:epidemiology; D011110:Polymorphism, Genetic; D012306:Risk; D012906:Smoke / Q000032:analysis*; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires; D014059:Tongue / Q000201:enzymology; D044465:White People / Q000235:genetics; D001741:Black or African American; D014026:Nicotiana
D002273:Carcinogens; D003062:Codon; D012906:Smoke; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7