Study of irinotecan-induced toxicity and its correlation to UGT1A1 gene promoter polymorphisms

Abstract

To investigate the distribution of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) gene promoter polymorphism and its relation to the toxicities caused by irinotecan in Chinese patients with cervical cancer and ovarian cancer. Sixty-four blood samples were taken from the patients with ovarian cancer and cervical cancer. The DNA was extracted and amplified with PCR. Then, the sequences of UGT1A1 gene promoter were detected by capillary electrophoresis allele fragment analysis (size-based analysis) methods. The relationship between UGT1A1 gene promoter polymorphism and the toxicity caused by irinotecan was analyzed. In all the patients, TA 6/6 was the most common genotype of UGT1A1 gene promoter (44 cases), accounting for 69% (44/64), followed by genotype of TA 6/7 (17 cases, 27%, 17/64), while genotype TA 7/7 was rare (3 cases, 5%, 3/64). The genotypes of UGT1A1 gene promoter was an independent factor for the occurrence of delayed diarrhea (P = 0.040, OR = 4.228, 95%CI: 1.065 - 16.785) but not for neutropenia (P = 0.068, OR = 3.659, 95%CI: 0.911 - 14.700). The patients with both genotype TA 6/7 and TA 7/7 presented much higher risk of delayed diarrhea and neutropenia than those with TA 6/6 (all P = 0.001). UGT1A1 gene promoter polymorphism may be a significant influencing factor for delayed diarrhea. The patients with both genotype TA 6/7 and TA 7/7 could present much higher risk for delayed diarrhea than those with TA 6/6, while genotype TA 6/6 may be the most common UGT1A1 promoter type in Chinese patients with cervical or ovarian cancer.