The Open Colorectal Cancer Journal

2009, 2 : 21-26
Published online 2009 August 19. DOI: 10.2174/1876820200902010021
Publisher ID: TOCOLCJ-2-21

Significant Correlation between Polymorphisms of UGT1A1 Gene and Low Irinotecan Toxicity in Colorectal Cancer Patients with FOLFIRI

Hsiang-Lin Tsai , Chin-Fan Chen , Chien-Yu Lu , Wei-Yu Fang , Deng-Chyang Wu , I-Chen Wu , Maw-Chang Sheen , Shiu-Ru Lin and Jaw-Yuan Wang
School of Medical and Health, Fooyin University, Kaohsiung, Taiwan and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou 1st Road, Kaohsiung 807, Taiwan.

ABSTRACT

Aim: To investigate the association between UDP-glucuronosyltransferase 1A1 (UGT1A1) genotypes and severe toxicity in Taiwanese patients with metastatic colorectal cancer (mCRC) receiving irinotecan chemotherapy.

Methods: We genotyped the UGT1A1 gene by direct sequencing. All the patients were evaluated to see whether the variant UGT1A1 genotype would correlate to severe toxicity of irinotecan consisting of grade III-IV neutropenia, diarrhea and nausea/vomiting. Genomic DNA was genotyped for UGT1A1, and patients were designated as 6/6, 6/7, or 7/7 depending on the number of TA repeats in the promoter region.

Results: The results showed that the genotype distribution of UGT1A1 in Taiwanese subjects differed significantly from that in Caucasians. Furthermore, patients with 6/7 or 7/7 genotype were associated with a higher incidence of grade III-IV neutropenia or diarrhea or nausea/vomiting (all p < 0.0001). The less frequencies of 6/7 and 7/7 genotypes may be responsible for the considerably lower occurrence of grade III-IV neutropenia and diarrhea in Taiwanese patients. Indeed, the UGT1A1 genotype was closely related to clinical response (p = 0.018).

Conclusion: UGT1A1 genotyping is a potential predictor of severe toxicity for Taiwanese mCRC patients treated with irinotecan chemotherapy, and may be useful to identify patients at-risk of toxicity, and thus could be used as a screening tool prior to therapy.

Keywords:

UGT1A1, irinotecan, toxicity.