Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142, China.
Med Oncol. 2013;30(3):630. doi: 10.1007/s12032-013-0630-8. Epub 2013 Jun 20.
The aim of this study was to investigate the associations between UDP-glucuronosyltransferase (UGT) 1A1 polymorphisms and irinotecan-induced toxicities in Chinese advanced gastric or esophageal cancer patients. The genotypes of UGT1A16 and UGT1A128 were analyzed by PCR amplification and Sanger sequencing in 42 gastric and 91 esophageal cancer patients receiving irinotecan-containing chemotherapy. The influences of UGT1A16/28 polymorphisms on severe diarrhea and neutropenia were analyzed. The overall incidence of UGT1A16/28 variants in gastric cancer and esophageal cancer was 38.1 % (GA: 31.0 %; AA: 6.9 %), 28.6 % (TA6/TA7: 26.2 %; TA7/TA7: 2.4 %) and 33.0 % (GA: 28.6 %; AA: 4.4 %), 25.3 % (TA6/TA7: 23.1 %; TA7/TA7: 2.2 %) in our cohort, respectively. A total of 10 patients (gastric cancer: 9.5 %, 4/42; esophageal cancer: 6.6 %, 6/91) had severe diarrhea and 35 patients (gastric cancer: 35.7 %, 15/42; esophageal cancer: 22.0 %, 20/91) had severe neutropenia. Statistic analysis between UGT1A1 genotyping and severe diarrhea was not conducted due to the limited number of patients. For gastric cancer, it seemed that only UGT1A16 variant was associated with severe neutropenia (P = 0.042), while among esophageal cancer patients, UGT1A16 (P = 0.011) or UGT1A128 (P = 0.026) variants were significantly associated with severe neutropenia. UGT1A16 variant was closely associated with severe neutropenia both in gastric cancer and in esophageal cancer, but the association between UGT1A1*28 variant and severe neutropenia in gastric and esophageal cancer was not consistent in this study, which would be validated in the future large samples.
本研究旨在探讨 UDP-葡萄糖醛酸基转移酶（UGT）1A1 多态性与中国晚期胃癌或食管癌患者伊立替康诱导毒性之间的关系。在 42 例接受伊立替康化疗的胃癌患者和 91 例食管癌患者中，通过 PCR 扩增和 Sanger 测序分析了 UGT1A16 和 UGT1A128 基因型。分析了 UGT1A16/28 多态性对严重腹泻和中性粒细胞减少的影响。胃癌和食管癌患者 UGT1A16/28 变异体的总发生率分别为 38.1%（GA：31.0%；AA：6.9%）、28.6%（TA6/TA7：26.2%；TA7/TA7：2.4%）和 33.0%（GA：28.6%；AA：4.4%）、25.3%（TA6/TA7：23.1%；TA7/TA7：2.2%）。本研究中共有 10 例（胃癌：9.5%，4/42；食管癌：6.6%，6/91）发生严重腹泻，35 例（胃癌：35.7%，15/42；食管癌：22.0%，20/91）发生严重中性粒细胞减少症。由于患者数量有限，未对 UGT1A1 基因分型与严重腹泻之间进行统计学分析。对于胃癌，似乎只有 UGT1A16 变异与严重中性粒细胞减少症相关（P = 0.042），而在食管癌患者中，UGT1A16（P = 0.011）或 UGT1A128（P = 0.026）变异与严重中性粒细胞减少症显著相关。UGT1A16 变异与胃癌和食管癌患者的严重中性粒细胞减少症密切相关，但本研究中 UGT1A1*28 变异与胃癌和食管癌患者严重中性粒细胞减少症的相关性不一致，这将在未来的大样本中得到验证。
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