Journal
ANTI-CANCER DRUGS
Volume 18, Issue 6, Pages 693-696Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0b013e32803a46fe
Keywords
bilirubin; ethnic distribution; irinotecan; sex distribution; UGT1A1; polymorphism
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The hepatic isoform 1A1 of uridine diphosphate glucuronosyltransferase is responsible for glucuronidation and detoxification of SN-38, the active metabolite of irinotecan. The presence of an additional TA repeat in the TATA sequence of the UGT1A1 promoter leads to a significant decrease in SN-38 glucuronidation. Patients with the UGT1A1 (TA)7 allele are more likely to experience severe neutropenia and diarrhea following irinotecan chemotherapy. We assessed the distribution of the UGT1A1 (TA), polymorphism in healthy male and female US residents of European and Asian descent. We used a fluorescent polymerase chain reaction-based assay to detect UGT1A1 (TA), polymorphisms in 138 healthy volunteers (56 Caucasians, 37 Chinese, 37 Filipino and eight Japanese) between the ages of 18 and 65 years. The chi(2)-test was used to assess between-group differences in the distribution of UGT1A1 (TA), genotypes. The UGT1A1 (TA)(6/6) genotype was significantly more common in Asians than in Caucasians (76 vs. 46%), whereas the (TA)(6/7) (39 vs. 20%) and (TA)(7/7) (13 vs. 5%) genotypes were more common in Caucasians than in Asians. Genotype distributions did not differ significantly between men and women in either group. The UGT1A1 (TA)(5/5) genotype was detected in one Caucasian woman. In conclusion, consistent with previous reports, the UGT1A1 (TA)(7/7) genotype was significantly more common in Caucasians than in Asians. UGT1A1 (TA)(n/n) genotype distribution did not vary with sex in individuals of European or Asian descent.
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