References
  1. Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. Oct 23 2014;371(17):1609-18. doi:10.1056/NEJMoa1403108
  2. Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. Mar 25 2000;355(9209):1041-7. doi:10.1016/s0140-6736(00)02034-1
  3. Slatter JG, Su P, Sams JP, Schaaf LJ, Wienkers LC. Bioactivation of the anticancer agent CPT-11 to SN-38 by human hepatic microsomal carboxylesterases and the in vitro assessment of potential drug interactions. Drug Metab Dispos. Oct 1997;25(10):1157-64.
  4. Innocenti F, Ratain MJ. Irinotecan treatment in cancer patients with UGT1A1 polymorphisms. Oncology (Williston Park). May 2003;17(5 Suppl 5):52-5.
  5. Mathijssen RH, van Alphen RJ, Verweij J, et al. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res. Aug 2001;7(8):2182-94.
  6. Guillemette C, Lévesque É, Rouleau M. Pharmacogenomics of human uridine diphospho-glucuronosyltransferases and clinical implications. Clin Pharmacol Ther. Sep 2014;96(3):324-39. doi:10.1038/clpt.2014.126
  7. de Jong FA, Scott-Horton TJ, Kroetz DL, et al. Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein. Clin Pharmacol Ther. Jan 2007;81(1):42-9. doi:10.1038/sj.clpt.6100019
  8. Bosma PJ, Chowdhury JR, Bakker C, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med. Nov 2 1995;333(18):1171-5. doi:10.1056/nejm199511023331802
  9. Jo JC, Lee JL, Ryu MH, et al. Phase II and UGT1A1 genotype study of irinotecan dose escalation as salvage therapy for advanced gastric cancer. Br J Cancer. May 8 2012;106(10):1591-7. doi:10.1038/bjc.2012.143
  10. Hu ZY, Yu Q, Pei Q, Guo C. Dose-dependent association between UGT1A1*28 genotype and irinotecan-induced neutropenia: low doses also increase risk. Clin Cancer Res. Aug 1 2010;16(15):3832-42. doi:10.1158/1078-0432.Ccr-10-1122.
  11. Zhou CF, Ma T, Su Y, et al. UGT1A1 gene polymorphisms and the toxicities of FOLFIRI in Chinese Han patients with gastrointestinal cancer. Anticancer Agents Med Chem. Feb 2013;13(2):235-41. doi:10.2174/1871520611313020008
  12. Liu CY, Chen PM, Chiou TJ, et al. UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities without affecting treatment outcome and survival in patients with metastatic colorectal carcinoma. Cancer. May 1 2008;112(9):1932-40. doi:10.1002/cncr.23370
  13. Iyer L, Das S, Janisch L, et al. UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J. 2002;2(1):43-7. doi:10.1038/sj.tpj.6500072
  14. Atasilp C, Chansriwong P, Sirachainan E, et al. Correlation of UGT1A1(*)28 and (*)6 polymorphisms with irinotecan-induced neutropenia in Thai colorectal cancer patients. Drug Metab Pharmacokinet. Feb 2016;31(1):90-94. doi:10.1016/j.dmpk.2015.12.004
  15. Toffoli G, Cecchin E, Corona G, et al. The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer. J Clin Oncol. Jul 1 2006;24(19):3061-8. doi:10.1200/jco.2005.05.5400
  16. Liu X, Cheng D, Kuang Q, Liu G, Xu W. Association of UGT1A1*28 polymorphisms with irinotecan-induced toxicities in colorectal cancer: a meta-analysis in Caucasians. Pharmacogenomics J. Apr 2014;14(2):120-9. doi:10.1038/tpj.2013.10
  17. Hoskins JM, Goldberg RM, Qu P, Ibrahim JG, McLeod HL. UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst. Sep 5 2007;99(17):1290-5. doi:10.1093/jnci/djm115
  18. Chen X, Liu L, Guo Z, et al. UGT1A1 polymorphisms with irinotecan-induced toxicities and treatment outcome in Asians with Lung Cancer: a meta-analysis. Cancer Chemother Pharmacol. Jun 2017;79(6):1109-1117. doi:10.1007/s00280-017-3306-9
  19. Mackenzie PI, Bock KW, Burchell B, et al. Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics. Oct 2005;15(10):677-85. doi:10.1097/01.fpc.0000173483.13689.56
  20. Cheng L, Li M, Hu J, et al. UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity: a system review and meta-analysis in Asians. Cancer Chemother Pharmacol. Mar 2014;73(3):551-60. doi:10.1007/s00280-014-2382-3
  21. Gao J, Zhou J, Li Y, Lu M, Jia R, Shen L. UGT1A1 6/28 polymorphisms could predict irinotecan-induced severe neutropenia not diarrhea in Chinese colorectal cancer patients. Med Oncol. 2013;30(3):604. doi:10.1007/s12032-013-0604-x
  22. Onoue M, Terada T, Kobayashi M, et al. UGT1A1*6 polymorphism is most predictive of severe neutropenia induced by irinotecan in Japanese cancer patients. Int J Clin Oncol. Apr 2009;14(2):136-42. doi:10.1007/s10147-008-0821-z
  23. Moriya H, Saito K, Helsby N, et al. Association between the low-dose irinotecan regimen-induced occurrence of grade 4 neutropenia and genetic variants of UGT1A1 in patients with gynecological cancers. Oncol Lett. Jun 2014;7(6):2035-2040. doi:10.3892/ol.2014.2046
  24. Han JY, Lim HS, Park YH, Lee SY, Lee JS. Integrated pharmacogenetic prediction of irinotecan pharmacokinetics and toxicity in patients with advanced non-small cell lung cancer. Lung Cancer. Jan 2009;63(1):115-20. doi:10.1016/j.lungcan.2007.12.003
  25. Jada SR, Lim R, Wong CI, et al. Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan-induced neutropenia in Asian cancer patients. Cancer Sci. Sep 2007;98(9):1461-7. doi:10.1111/j.1349-7006.2007.00541.x
  26. Okuyama Y, Hazama S, Nozawa H, et al. Prospective phase II study of FOLFIRI for mCRC in Japan, including the analysis of UGT1A1 28/6 polymorphisms. Jpn J Clin Oncol. Apr 2011;41(4):477-82. doi:10.1093/jjco/hyr001
  27. Yang C, Liu Y, Xi WQ, et al. Relationship between UGT1A1*6/*28 polymorphisms and severe toxicities in Chinese patients with pancreatic or biliary tract cancer treated with irinotecan-containing regimens. Drug Des Devel Ther. 2015;9:3677-83. doi:10.2147/dddt.S86750
  28. Hirasawa A, Zama T, Akahane T, et al. Polymorphisms in the UGT1A1 gene predict adverse effects of irinotecan in the treatment of gynecologic cancer in Japanese patients. J Hum Genet. Dec 2013;58(12):794-8. doi:10.1038/jhg.2013.105
  29. Kimura K, Yamano T, Igeta M, et al. UGT1A1 polymorphisms in rectal cancer associated with the efficacy and toxicity of preoperative chemoradiotherapy using irinotecan. Cancer Sci. Dec 2018;109(12):3934-3942. doi:10.1111/cas.13807
  30. Horikawa N, Baba T, Matsumura N, et al. Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients. BMC Cancer. Oct 19 2015;15:739. doi:10.1186/s12885-015-1703-1
  31. Bai Y, Wu HW, Ma X, Liu Y, Zhang YH. Relationship between UGT1A1*6/*28 gene polymorphisms and the efficacy and toxicity of irinotecan-based chemotherapy. Onco Targets Ther. 2017;10:3071-3081. doi:10.2147/ott.S137644
  32. Treenert A, Areepium N, Tanasanvimon S. Effects of ABCC2 and SLCO1B1 Polymorphisms on Treatment Responses in Thai Metastatic Colorectal Cancer Patients Treated with Irinotecan-Based Chemotherapy. Asian Pac J Cancer Prev. Oct 26 2018;19(10):2757-2764. doi:10.22034/apjcp.2018.19.10.2757
  33. Haenisch S, Zimmermann U, Dazert E, et al. Influence of polymorphisms of ABCB1 and ABCC2 on mRNA and protein expression in normal and cancerous kidney cortex. Pharmacogenomics J. Feb 2007;7(1):56-65. doi:10.1038/sj.tpj.6500403
  34. Han JY, Lim HS, Yoo YK, et al. Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer. Cancer. Jul 1 2007;110(1):138-47. doi:10.1002/cncr.22760
  35. Atasilp C, Chansriwong P, Sirachainan E, et al. Effect of drug metabolizing enzymes and transporters in Thai colorectal cancer patients treated with irinotecan-based chemotherapy. Sci Rep. Aug 10 2020;10(1):13486. doi:10.1038/s41598-020-70351-0
  36. Han FF, Guo CL, Yu D, et al. Associations between UGT1A1*6 or UGT1A1*6/*28 polymorphisms and irinotecan-induced neutropenia in Asian cancer patients. Cancer Chemother Pharmacol. Apr 2014;73(4):779-88. doi:10.1007/s00280-014-2405-0
  37. Yang Y, Zhou M, Hu M, et al. UGT1A1*6 and UGT1A1*28 polymorphisms are correlated with irinotecan-induced toxicity: A meta-analysis. Asia Pac J Clin Oncol. Oct 2018;14(5):e479-e489. doi:10.1111/ajco.13028
  38. Zhang X, Yin JF, Zhang J, Kong SJ, Zhang HY, Chen XM. UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis. Cancer Chemother Pharmacol. Jul 2017;80(1):135-149. doi:10.1007/s00280-017-3344-3
  39. Chen YJ, Hu F, Li CY, et al. The association of UGT1A1*6 and UGT1A1*28 with irinotecan-induced neutropenia in Asians: a meta-analysis. Biomarkers. Feb 2014;19(1):56-62. doi:10.3109/1354750x.2013.867534
  40. Zhu X, Ma R, Ma X, Yang G. Association of UGT1A1*6 polymorphism with irinotecan-based chemotherapy reaction in colorectal cancer patients: a systematic review and a meta-analysis. Biosci Rep. Oct 30 2020;40(10)doi:10.1042/bsr20200576
  41. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Cochrane Handbook for Systematic Reviews of Interventions version 6.0. Available online: www.training.cochrane.org/handbook (assessed on 15 July 2021)
  42. Wells, G., Shea, B., O’Connell, D., & Peterson, J. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, ON: Ottawa Hospital Research Institute. Available online: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed on 15 July 2021).
  43. Biswas M, Kali MSK, Biswas TK, Ibrahim B. Risk of major adverse cardiovascular events of CYP2C19 loss-of-function genotype guided prasugrel/ticagrelor vs clopidogrel therapy for acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis. Platelets. Jul 4 2021;32(5):591-600. doi:10.1080/09537104.2020.1792871
  44. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. Nov 1 1997;127(9):820-6. doi:10.7326/0003-4819-127-9-199711010-00008
  45. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. Bmj. Sep 6 2003;327(7414):557-60. doi:10.1136/bmj.327.7414.557
  46. Sutton AJ, Duval SJ, Tweedie RL, Abrams KR, Jones DR. Empirical assessment of effect of publication bias on meta-analyses. Bmj. Jun 10 2000;320(7249):1574-7. doi:10.1136/bmj.320.7249.1574
  47. Ando K, Emi Y, Suenaga T, et al. A prospective study of XELIRI plus bevacizumab as a first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101). Int J Clin Oncol. Oct 2017;22(5):913-920. doi:10.1007/s10147-017-1140-z
  48. Bandyopadhyay A, Sharma S, Behera D, Singh N. UGT1A1 Gene Polymorphisms in Patients with Small Cell Lung Cancer Treated with Irinotecan-Platinum Doublet Chemotherapy and Their Association with Gastrointestinal Toxicity and Overall Survival. Oncologist. Mar 16 2021;doi:10.1002/onco.13757
  49. Choi YH, Kim TW, Kim KP, et al. A Phase II study of clinical outcomes of 3-week cycles of irinotecan and S-1 in patients with previously untreated metastatic colorectal cancer: influence of the UGT1A1 and CYP2A6 polymorphisms on clinical activity. Oncology. 2012;82(5):290-7. doi:10.1159/000337989
  50. Deng B, Jia L, Tan H, et al. Effects of Shengjiangxiexin decoction on irinotecan-induced toxicity in patients with UGT1A1*28 and UGT1A1*6 polymorphisms. J Tradit Chin Med. Feb 2017;37(1):35-42. doi:10.1016/s0254-6272(17)30024-9
  51. Gao J, Zhou J, Li Y, et al. Associations between UGT1A1*6/*28 polymorphisms and irinotecan-induced severe toxicity in Chinese gastric or esophageal cancer patients. Med Oncol. 2013;30(3):630. doi:10.1007/s12032-013-0630-8
  52. Minami H, Sai K, Saeki M, et al. Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Pharmacogenet Genomics. Jul 2007;17(7):497-504. doi:10.1097/FPC.0b013e328014341f
  53. Liu D, Li J, Gao J, Li Y, Yang R, Shen L. Examination of multiple UGT1A and DPYD polymorphisms has limited ability to predict the toxicity and efficacy of metastatic colorectal cancer treated with irinotecan-based chemotherapy: a retrospective analysis. BMC Cancer. Jun 20 2017;17(1):437. doi:10.1186/s12885-017-3406-2
  54. Matsuoka H, Murakami R, Abiko K, et al. UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy: a retrospective study. BMC Cancer. Aug 5 2020;20(1):729. doi:10.1186/s12885-020-07225-1
  55. Li M, Wang Z, Guo J, et al. Clinical significance of UGT1A1 gene polymorphisms on irinotecan-based regimens as the treatment in metastatic colorectal cancer. Onco Targets Ther. 2014;7:1653-61. doi:10.2147/ott.S67867
  56. Nakamura Y, Soda H, Oka M, et al. Randomized phase II trial of irinotecan with paclitaxel or gemcitabine for non-small cell lung cancer: association of UGT1A1*6 and UGT1A1*27 with severe neutropenia. J Thorac Oncol. Jan 2011;6(1):121-7. doi:10.1097/JTO.0b013e318200e4e8
  57. Park SR, Kong SY, Rhee J, et al. Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results. Ann Oncol. Apr 2011;22(4):890-896. doi:10.1093/annonc/mdq435
  58. Peng H, Duan Z, Pan D, Wen J, Wei X. UGT1A1 Gene Polymorphism Predicts Irinotecan-Induced Severe Neutropenia and Diarrhea in Chinese Cancer Patients. Clin Lab. Sep 1 2017;63(9):1339-1346. doi:10.7754/Clin.Lab.2017.170105
  59. Satoh T, Ura T, Yamada Y, et al. Genotype-directed, dose-finding study of irinotecan in cancer patients with UGT1A1*28 and/or UGT1A1*6 polymorphisms. Cancer Sci. Oct 2011;102(10):1868-73. doi:10.1111/j.1349-7006.2011.02030.x
  60. Shi Y, Hu Y, Hu X, Li X, Lin L, Han X. Cisplatin combined with irinotecan or etoposide for untreated extensive-stage small cell lung cancer: A multicenter randomized controlled clinical trial. Thorac Cancer. Nov 2015;6(6):785-91. doi:10.1111/1759-7714.12303
  61. Chen S, Hua L, Feng C, et al. Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang. BMC Gastroenterol. Apr 7 2020;20(1):96. doi:10.1186/s12876-020-01227-w
  62. Sunakawa Y, Ichikawa W, Fujita K, et al. UGT1A1*1/*28 and *1/*6 genotypes have no effects on the efficacy and toxicity of FOLFIRI in Japanese patients with advanced colorectal cancer. Cancer Chemother Pharmacol. Aug 2011;68(2):279-84. doi:10.1007/s00280-010-1485-8
  63. Takahara N, Nakai Y, Isayama H, et al. Uridine diphosphate glucuronosyl transferase 1 family polypeptide A1 gene (UGT1A1) polymorphisms are associated with toxicity and efficacy in irinotecan monotherapy for refractory pancreatic cancer. Cancer Chemother Pharmacol. Jan 2013;71(1):85-92. doi:10.1007/s00280-012-1981-0
  64. Takano M, Kato M, Yoshikawa T, et al. Clinical significance of UDP-glucuronosyltransferase 1A1*6 for toxicities of combination chemotherapy with irinotecan and cisplatin in gynecologic cancers: a prospective multi-institutional study. Oncology. 2009;76(5):315-21. doi:10.1159/000209335
  65. Yamaguchi T, Iwasa S, Shoji H, et al. Association between UGT1A1 gene polymorphism and safety and efficacy of irinotecan monotherapy as the third-line treatment for advanced gastric cancer. Gastric Cancer. Jul 2019;22(4):778-784. doi:10.1007/s10120-018-00917-5
  66. Wang Y, Shen L, Xu N, et al. UGT1A1 predicts outcome in colorectal cancer treated with irinotecan and fluorouracil. World J Gastroenterol. Dec 7 2012;18(45):6635-44. doi:10.3748/wjg.v18.i45.6635
  67. Wang Y, Yi C, Wang Y, et al. Distribution of uridine diphosphate glucuronosyltransferase 1A polymorphisms and their role in irinotecan-induced toxicity in patients with cancer. Oncol Lett. Nov 2017;14(5):5743-5752. doi:10.3892/ol.2017.6933
  68. Xiao XG, Xia S, Zou M, et al. The relationship between UGT1A1 gene polymorphism and irinotecan effect on extensive-stage small-cell lung cancer. Onco Targets Ther. 2015;8:3575-83. doi:10.2147/ott.S95149
  69. Xu C, Tang X, Qu Y, Keyoumu S, Zhou N, Tang Y. UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer. Cancer Chemother Pharmacol. Jul 2016;78(1):119-30. doi:10.1007/s00280-016-3057-z
  70. Ma X, Han S, Liu Y, Liu JT, Fang J, Zhang YH. Pharmacogenetic impact of UGT1A1 polymorphisms on pulmonary neuroendocrine tumours treated with metronomic irinotecan-based chemotherapy in Chinese populations. J Pharm Pharmacol. Nov 2020;72(11):1528-1535. doi:10.1111/jphp.13333
  71. Xu Q, Ding YY, Song LX, Xu JF. Correlation of UGT1A1 and ERCC1 gene polymorphisms with the outcome of combined irinotecan plus cisplatin treatment in recurrent ovarian cancer. Genet Mol Res. Jun 29 2015;14(2):7241-7. doi:10.4238/2015.June.29.17
  72. Yamamoto N, Takahashi T, Kunikane H, et al. Phase I/II pharmacokinetic and pharmacogenomic study of UGT1A1 polymorphism in elderly patients with advanced non-small cell lung cancer treated with irinotecan. Clin Pharmacol Ther. Feb 2009;85(2):149-54. doi:10.1038/clpt.2008.152
  73. Lu YY, Huang XE, Wu XY, et al. Clinical observations on associations between the UGT1A1 genotype and severe toxicity of irinotecan. Asian Pac J Cancer Prev. 2014;15(7):3335-41. doi:10.7314/apjcp.2014.15.7.3335
  74. Yun F, Lulu M, Zhiyu H, et al. Uridine diphosphate glucuronide transferase 1A1FNx0128 gene polymorphism and the toxicity of irinotecan in recurrent and refractory small cell lung cancer. J Cancer Res Ther. Nov 2014;10 Suppl:C195-200. doi:10.4103/0973-1482.145871.
  75. Dean L. Irinotecan Therapy and UGT1A1 Genotype. Available from: https://www.ncbi.nlm.nih.gov/books/NBK294473/ (accessed on 15 July 2021).
  76. Fukui T, Mitsufuji H, Kubota M, et al. Prevalence of topoisomerase I genetic mutations and UGT1A1 polymorphisms associated with irinotecan in individuals of Asian descent. Oncol Lett. Sep 1 2011;2(5):923-928. doi:10.3892/ol.2011.346
Table 1 . Baseline characteristics of included studies