结直肠癌组织中ARID1A基因突变和MSH2蛋白表达与临床病理特征及预后的相关性

目的:检测结直肠癌（CRC）组织中富含AT结合域1A（ARID1A）基因突变和 mutS同种组织蛋白2(MSH2)蛋白表达,分析两者的临床意义。方法:选取自2017年1月至2018年1月期间我院诊治的142例CRC患者作为研究对象。采用直接测序法检测CRC癌组织中ARID1A基因突变。免疫组化检测癌及癌旁组织MSH2蛋白表达。Spearman秩相关分析ARID1A基因突变和MSH2蛋白表达的相关性。统计学分析ARID1A基因突变、MSH2蛋白表达与CRC临床病理特征的关系。Kaplan-Meier生存分析ARID1A基因突变和MSH2蛋白表达对患者生存预后的影响。单因素及多因素Cox回归分析影响CRC患者生存预后的因素。结果:142例CRC癌组织中,27例发生ARID1A基因突变,ARID1A基因突变率为19.01%（27/142）。MSH2棕黄色阳性表达主要位于细胞核。CRC癌组织中MSH2阳性率为51.41%（73/142）,明显低于癌旁组织91.55%（130/142）（χ2=56.116,P=0.000）。不同肿瘤TNM分期、淋巴结转移CRC癌组织中ARID1A基因突变、MSH2阳性率差异具有统计学意义（P＜0.05）。CRC癌组织中ARID1A基因突变和MSH2表达呈显著负相关性(r=-0.575,P=0.000)。ARID1A基因突变组患者3年总体生存率为37.04%（10/27）,明显低于野生型组患者67.27%（74/110）（P=0.000）;MSH2阳性表达组患者3年总体生存率为81.43%（57/70）,明显高于阴性表达组患者42.30%（27/67）（P=0.000）。ARID1A基因突变型、MSH2阴性表达、肿瘤TNM分期Ⅲ期及伴淋巴结转移是影响CRC患者预后的独立危险因素（P＜0.05）。结论:ARID1A基因、MSH2表达与CRC患者肿瘤分期及淋巴结转移有关,是CRC患者预后预测的独立因素。     

ARID1A基因突变或失表达介导肿瘤发生的机制及其在胃癌免疫治疗中的价值

AT丰富结合域1A（AT-rich interactive domain 1A,ARID1A）是染色质重塑复合体SWI/SNF（SWItch/Sucrose non-ferment-able）的一个亚基,它是所有肿瘤中突变最频繁的染色质调节因子之一,这些突变大部分是移码或无义突变。ARID1A是一个抑癌基因,它的突变或失表达可能从不同的途径导致肿瘤的发生发展。同时,ARID1A突变或表达缺失与胃癌程序性死亡受体-配体1（programmed cell death-ligand 1,PD-L1）高表达、EB病毒（Epstein-Barr virus,EBV）阳性、微卫星高度不稳定性（microsatellite insta-bility-high,MSI-H）、高肿瘤突变负荷（tumor mutation burden,TMB）及较多的肿瘤浸润淋巴细胞（tumor infiltrating lymphocytes,TILs）相关,且免疫检查点抑制剂（immune checkpoint inhibitors,ICIs）可以明显延长ARID1A缺失的肿瘤患者的无进展生存期。本文就ARID1A基因突变或失表达导致肿瘤发生可能途径及其与胃癌免疫治疗的关系进行综述。      

ARID1A蛋白在胃癌组织中的表达及临床意义

目的:探讨ARID1A蛋白异常表达与胃癌的临床病理特征及患者预后的关系.方法:采用免疫组织化学方法检测82例正常胃黏膜组织、25例肠上皮化生和133例胃癌组织中ARID1A蛋白的表达情况.结果:ARID1A蛋白在胃癌组织中的缺失率(42.1％)显著高于正常胃黏膜组织(22.0％)和肠上皮化生组织(24.0％),表达差异有统计学意义(P＜0.05).ARID1A蛋白的缺失表达与胃癌原发瘤浸润深度、淋巴结转移及远处转移显著相关(P均＜0.05),且ARID1 A蛋白的缺失表达率与胃癌的TNM分期期别成正相关(-=0.201,P＜0.05),与胃癌患者的性别、年龄、肿瘤大小、组织学分型和Lauren分型无关(P＞0.05).ARID1A蛋白表达缺失组的胃癌患者生存时间显著短于阳性组,预后差(x2=10.169,P=0.001),多因素Cox回归分析结果显示,ARID1A蛋白表达缺失、肿瘤原发灶大小和TNM分期是影响胃癌患者预后的独立危险因素.结论:AR-ID1A蛋白在胃癌组织中表达缺失和与胃癌临床病理特征的关系结果表明,其可能作为一个重要的抑癌基因对抑制胃癌的发生发展及转移有重要作用.     

ARID1A及PTEN在乳腺癌组织中的表达及其与临床病理特征的相关性

目的:探讨乳腺癌组织中ARID1A及PTEN的表达情况,并分析其与乳腺癌患者临床病理特征的相关性。方法:收集2015年7月至2019年12月就诊于我院并经病理科诊断为乳腺癌92例、乳腺纤维腺瘤55例及癌周正常乳腺组织38例,采用免疫组化染色方法EnVision二步法检测各组中ARID1A及PTEN的表达水平,并分析二者在各组间表达的差异性及相关性;将乳腺癌组按照临床病理特征进行分组,统计分析这两种蛋白在各组间表达的差异性及与预后相关性。结果:浸润性乳腺癌组织中ARID1A及PTEN的阳性表达率低于乳腺纤维腺瘤及癌周正常乳腺组织,且差异有统计学意义(P<0.05);ARID1A及PTEN的表达与乳腺癌患者的年龄、肿瘤大小、分子分型、远处转移等因素均无相关性(P＞0.05);ARID1A的表达与组织学分级、T分期及脉管侵犯有关,而PTEN与淋巴结转移、神经侵犯、脉管侵犯有关(P<0.05)。实验结果还显示ARID1A和PTEN蛋白在乳腺癌中的表达呈正相关（r=0.243,P<0.05）;ARID1A及PTEN蛋白表达缺失组的乳腺癌患者生存期明显短于阳性组乳腺癌患者,预后较差。结论:ARID1A及 PTEN在乳腺癌中均存在低表达的状态,并与肿瘤的脉管侵犯、高级别组织学分级等恶性生物学特征间存负向关联性,有望成为提示乳腺癌预后的两项可供参考的生物学指标。     

非髓性白血病的其他恶性血液病中DNMT3A基因突变的检测及临床意义

目的:了解DNMT3A基因突变在非髓性白血病的其他恶性血液肿瘤患者中的发生率、分布情况及临床意义.方法:选取196例非髓性白血病的其他血液肿瘤患者为研究对象,提取患者外周血基因组DNA,针对DNMT3A基因突变热点R882位点设计引物,采用聚合酶链式反应(PCR)法扩增DNMT3A基因23号外显子整个编码区基因片段,再将扩增产物纯化后测序,分析DNMT3A基因突变在本组恶性血液病患者中的发生率、分布情况及临床意义.结果:在57例非霍奇金淋巴瘤及34例骨髓增生异常综合征患者中各检出1例伴DNMT3A基因突变,在25例急性淋巴细胞白血病、45例多发性骨髓瘤和35例骨髓增殖性肿瘤患者中均未检测到DNMT'3A基因突变.结论:非髓性白血病的其他血液肿瘤患者中DNMT3A基因突变少见,伴DNMT3A基因突变的1例T淋巴母细胞白血病/淋巴瘤患者预后不良,联合去甲基化药物的化疗方案使伴该基因突变的1例骨髓增生异常综合征患者一度获得血液学完全缓解,但短期内转为急性白血病并发严重感染死亡.     

富AT结合域蛋白1A在乳腺癌中的表达及其预后意义

目的旨在通过检测富AT结合域蛋白1A(ARID1A)在乳腺良恶性肿瘤中的表达差异,探讨其对患者预后的影响。方法用随机数字表法选取北京电力医院2009年1月至2015年5月乳腺浸润性导管癌和乳腺纤维腺瘤术后标本各50例,采用免疫组织化学En Vision法检测ARID1A的表达差异。分析ARID1A的表达与乳腺癌患者临床病理参数的关系。以电话及病案查阅的方式了解乳腺癌患者的预后情况,随访日期截止至2015年12月31日,计算出DFS和OS。ARID1A、HER-2、ER和P53间的相关性研究采用非参数Spearman检验。采用Kaplan-Meier法进行生存分析,Log-rank检验进行生存率比较,同时Cox比例风险回归模型解析影响预后的多种因素。结果 ARID1A在50例乳腺浸润性导管癌中高表达率为46%(23/50),在50例纤维腺瘤中高表达率为72%(36/50),差异有统计学意义(χ~2=6.986,P=0.008)。在不同母乳喂养时间、组织学分级、P53表达、ER表达、PR表达、分子分型、HER-2表达的患者中ARID1A的表达差异亦有统计学意义(χ~2=4.177、4.726、4.177、5.469、14.661、5.469,P均0.050)。ARID1A的表达与P53的表达呈正相关(r=0.289,P=0.042),与ER的表达呈正相关(r=0.331,P=0.019),而与HER-2的表达呈负相关(r=-0.372,P=0.008)。TNMⅠ、Ⅱ期患者的3年DFS高于TNMⅢ、Ⅳ期(85.5%比42.4%,χ~2=9.657,P=0.002),肿瘤直径≤2 cm的患者的5年OS高于肿瘤直径2 cm的患者(100%比71.3%,χ~2=5.598,P=0.018),P53阳性组的3年DFS和5年OS均高于P53阴性组(86.3%比45.5%,χ~2=5.077,P=0.024;95.2%比50.8%,χ~2=9.476,P=0.002),ARID1A高表达患者的3年DFS和5年OS均高于ARID1A低表达患者(81.8%比70.2%,χ~2=0.454,P=0.500;90.9%比76.1%,χ~2=0.090,P=0.765)。多变量Cox回归模型可见P53阳性表达为影响乳腺癌患者OS的独立保护性因素(P=0.028,OR=0.079,95%CI:0.008~0.761),ARID1A的表达不是影响OS的独立预后因素(P=0.194,OR=4.758,95%CI:0.453~49.957)。结论 ARID1A在乳腺癌组织中的表达低于乳腺纤维腺瘤,可能对乳腺癌的发生发展起重要作用。     

CD133、SPARC和ARID1A在胃癌中的表达及临床意义

目的 探讨CD133、富含半胱氨酸的酸性分泌蛋白（SPARC）和AT丰富结构域1A（ARID1A）在胃癌组织中的表达及其与临床病理特征和预后的关系。方法 采用免疫组化法检测90例胃癌组织中CD133、SPARC和ARID1A的表达情况,分析其与胃癌临床病理特征及预后的关系。结果 胃癌组织中CD133、SPARC和ARIDIA的阳性表达率分别为26. 7％（24／90）、72.2％（65／90）和30.0％（27／90）。3种蛋白的表达与性别、年龄、肿瘤大小均无关,与TNM分期有关（P＜0.05）。ARID1A的表达与肿瘤浸润深度、分化程度相关（P＜0.05）;CD133的表达与分化程度、脉管侵犯、淋巴结转移、肿瘤原发部位有关（P＜0.05）;SPARC的表达与淋巴结转移及脉管侵犯有关（P＜0.05）。Cox多因素分析显示,TNM分期、术后辅助化疗周期、ARID1A和SPARC的表达是影响患者无病生存期（DFS）的独立因素,而TNM分期、术后辅助化疗周期及CD133的表达是影响总生存期（OS）的独立预后因素。CD133阳性表达者的中位DFS和OS分别为12个月和17个月,阴性表达者分别为41个月和55个月,差异均有统计学意义（P＜0.05）。SPARC高表达者的中位DFS和OS分别为41个月和54个月,高于低表达者的10个月和25个月,差异均有统计学意义（P＜0.05）。ARID1A阳性表达者的中位DFS和OS未达,阴性表达者分别为20个月和37个月,差异均有统计学意义（P＜0.05）。结论 CD133、SPARC、ARID1A可能在胃癌的发生、侵袭、转移中发挥重要作用,检测其在胃癌组织中的表达,有助于判断预后,为胃癌治疗提供依据。     

潜在类别模型在ARID1A基因低频变异与原发性肝癌遗传关联中的应用

目的应用潜在类别模型分析ARID1A基因低频变异与原发性肝癌的关系。方法根据基因的不同功能区域将ARID1A基因低频变异进行合并, 应用潜在类别模型分析合并后的ARID1A基因低频变异得到分类潜变量, 采用logistic回归分析ARID1A基因低频变异与肝癌发生之间的关系。结果潜在类别模型将ARID1A基因低频变异人群分为3类, 类别1主要为基因未突变人群, 占比94.2%(2 452/2 603);类别2主要为基因转录调控功能区突变人群, 占比4.8%(124/2 603);类别3主要为基因外显子突变人群, 占比1.0%(27/2 603)。以类别1人群作为参照, 转录调控功能区基因突变可降低肝癌的发生风险(OR为0.601, 95%CI为0.364～0.992,P=0.046)。结论潜在类别模型可识别肝癌相关基因低频变异, 潜在类别模型可推广应用于更多复杂疾病相关低频变异的遗传关联研究。     

miR-765靶向ARID1A对结直肠癌细胞侵袭及迁移的影响

目的 探讨微小核糖核酸-765(miR-765)靶向AT丰富结合域蛋白1A(ARID1A)对结直肠癌细胞侵袭及迁移的影响。方法 收集35例结直肠癌患者的结直肠癌组织及癌旁组织,体外培养结直肠癌SW480细胞并分为对照组、siRNA NC组、miR-765 siRNA组、mimic NC组和miR-765 mimic组。qRT-PCR法检测miR-765、ARID1A mRNA表达,Transwell法检测SW480细胞迁移和侵袭情况,蛋白印迹法检测ARID1A、基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)蛋白表达,双荧光素酶实验检测miR-765与ARID1A的靶向关系。结果 与癌旁组织相比,结直肠癌组织中miR-765水平显著升高,ARID1A mRNA及蛋白水平显著降低(P＜0.001),且结直肠癌组织中miR-765与ARID1A mRNA呈显著负相关(r=-0.768,P＜0.001);与TNM分期为Ⅰ~Ⅱ期的患者相比,Ⅲ~Ⅳ期的患者结直肠癌组织中miR-765水平显著升高(P＜0.01),ARID1A蛋白水平显著降低(P＜0.001)。敲减miR-765表达后SW480细胞迁移数、侵袭数、miR-765水平及MMP-9、VEGF蛋白水平显著降低,ARID1A水平显著升高(P＜0.05);过表达miR-765后SW480细胞迁移数、侵袭数、miR-765水平及MMP-9、VEGF蛋白水平显著升高,ARID1A水平显著降低(P＜0.05)。miR-765靶向调控ARID1A表达。结论 miR-765可能通过靶向抑制ARID1A表达,促进结直肠癌SW480细胞的侵袭和迁移过程。     

基于二代测序技术探究胃癌中医证型的基因突变特征

摘 要：［目的］利用二代测序技术研究胃癌中医证型的基因突变特征，从肿瘤基因组层面初步探索胃癌中医证候的客观化指标，指导临床精准治疗。［方法］收集临床病理分期为Ⅰ~Ⅳ期且未经任何治疗的胃癌患者，根据2011年《胃癌中医诊疗方案》进行辨证分型，采用二代测序技术（含450个肿瘤相关突变基因）检测肿瘤细胞的基因突变情况，结合临床资料和中医证型进行生物信息学分析，从而探究胃癌中医证型的基因突变特点。［结果］共有130例Ⅰ～Ⅳ期胃癌患者纳入本研究，辨证分型为脾气虚证、血虚证、热毒证等共8个单证。对中医单证和测序获得的363个突变基因进行分析，得到与各单证相关的高频和驱动基因，脾气虚证多见ARID1A、PIK3CA、APC基因突变；血虚证多见KMT2C基因突变；热毒证多见TGFBR2、HNF1A、ERBB3、KMT2D基因突变。130例患者中共有92例携带与单证证型相关的突变基因，采用无监督层次聚类分析得到脾虚热毒证这一特征证型，该复合证型多有Hippo、TGF-β等信号通路的激活，表现为微卫星高度不稳定（MSI-H）和高肿瘤突变负荷（TMB）的特点。［结论］不同单证的胃癌患者具有不同的基因突变特征，脾气虚证多有PIK3CA、ARID1A、APC基因突变；新发胃癌患者多为虚实夹杂的复合证型，辨证为脾虚热毒证的胃癌患者可能是免疫治疗的适宜人群。     

CYP1A1.

CYP1A1 plays an important role in the metabolism of polycyclic hydrocarbons that occur in the environment and several studies suggest that the genetic polymorphism of the gene may play a role in the predisposition to cancer. In order to evaluate the function of CYP1A1 in vivo as a host factor determinant of environmentally-caused cancers in humans, additional investigations are needed involving not only molecular epidemiological approaches in different ethnic populations but also more direct approaches such as the use of gene-targeted mice as a model system.     

Linkage disequilibrium of UGT1A1 *6 and UGT1A1 *28 in relation to UGT1A6 and UGT1A7 polymorphisms

UDP-glucuronosyltransferase (UGT) enzymes are responsible for the glucuronidation and detoxification of many endogenous or exogenous xenobiotics. Gilbert's syndrome (GS) and Crigler Najjar syndrome type 2 (CNS-II) are characterized by unconjugated hyperbilirubinemia due to reduced enzymatic activity of UGT1A1. Recent studies have demonstrated the frequent co-existence of UGT1A1 *28 (-53 [TA]6>7) with other polymorphisms of UGT1A6 and UGT1A7. This finding suggests the occurrence of linkage disequilibrium (LD) among UGT1A1, UGT1A6 and UGT1A7 polymorphisms. UGT1A1 *6 (211G>A, G71R) and UGT1A1 *28 are common in Asian populations. In the present study, we investigated the LD of UGT1A1 *6 and UGT1A1 *28 in relation to UGT1A6 and UGT1A7 polymorphisms. Exon 1 of UGT1A1, UGT1A6 and UGT1A7 was sequenced using genomic DNA isolated from peripheral leukocytes of 390 Japanese subjects. LD and haplotypes were analyzed using SNPAlyze ver. 5.0 software. UGT1A1 *6 had a strong LD in relation to UGT1A6 variants including 541A>G and 552A>C (D'=0.846-0.848, r(2)=0.413-0.438) and UGT1A7 variants including 387T>G, 391C>A, 392G>A and 622T>C (D'=0.667-0.858, r(2)=0.207-0.413). UGT1A1 *28 had a lower degree of LD than UGT1A1 *6 in relation to these variants (D'=0.245-0.401, r(2)=0.025-0.063). All the haplotypes with G71R lacked -53[TA]6>7. The present study showed for the first time that the LD of UGT1A1 *6 in relation to UGT1A6 and 1A7 polymorphisms is far stronger than UGT1A1 *28. The UGT1A1 *6 allele appears to be independent of the UGT1A1 *28 allele. Although patients with GS and CNS-II are believed to have good prognosis, a subgroup of GS or CNS-II patients with the UGT1A1 *6 polymorphism might be at risk of abnormal drug metabolism and of developing malignant disease.     

A novel CYP1A1 gene polymorphism in African-Americans

A new Mspl RFLP in the CYP1A1 gene has been found in genomicDNA from African-Americans. The polymorphism results from asingle A-T to G-C transition in the 3' noncoding region {smalltilde}300 bp upstream from the polyadenylation site. This mutationleads to cleavage of the normal 2.3 kb Mspl restriction fragmentinto 1.3 and 1.0 kb fragments. The heterozygous mutation hasbeen seen in 8 of 47 African-Americans, but was not detectedin 191 Caucasians or 30 Asians. No linkage was observed witheither of the two previously described polymorphisms in thisgene.     

CYP1A1, SULT1A1, and SULT1E1 polymorphisms are risk factors for endometrial cancer susceptibility

BACKGROUND: In estrogen biosynthetic pathways, many enzymes are important for metabolism, detoxification, and bioavailability. Polymorphisms in these genes may have an effect on the enzymes' function. For example, higher expression and activation of biosynthetic enzymes and lower expression and activation of conjugation enzymes may lead to high toxicity or carcinogenesis. The authors hypothesized that single nucleotide polymorphisms (single nucleotide polymorphisms) of CYP1A1, CYP1A2, CYP1B1, CYP17, SULT1A1, SULT1E1, and SHBG genes may be risk factors for endometrial cancer. METHODS: DNA samples from 150 cases of endometrial cancer and healthy controls (n = 165) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypic frequency of 13 different polymorphic loci on the CYP1A1 (m1, m2, m3, m4), CYP1A2 1F, CYP1B1 codon432, COMT codon158, CYP17, SULT1A1 (Arg213His, 14A/G, 85C/T in the 3' flanking region), SULT1E1-64G/A promoter region, and SHBG genes. Genotyping was validated by direct DNA sequencing. The authors also investigated the relation between expression of CYP1A1 in endometrial cancer tissues and genotypes of CYP1A1 m1. RESULTS: A decreased frequency of TC + CC genotype of the CYP1A1 m1 (T/C) polymorphism was observed in endometrial cancer patients compared with controls (OR = 0.42; 95% CI, 0.27-0.69). The T-A haplotype of CYP1A1 m1 and m2 was increased in endometrial cancer patients (P = .017). The frequency of CYP1A1 m1 T/C + C/C was higher in a high CYP1A1 expression group (P = .009). The authors also found that individuals carrying the variants of SULT1A1 codon213 and 2 single nucleotide polymorphisms in the 3' flanking region (14A/G and 85C/T) had an increased risk for endometrial cancer. The frequencies of G-A-C and A-G-T haplotypes of these 3 variants were higher in endometrial cancer patients (P < .0001; P = .0002). In addition, the frequency of combined genotypes (SULT1A1 213 GA + AA and CYP1A1 m1 TT) was higher in endometrial cancer patients. (OR, 4.58; 95% CI, 2.35-8.93). CONCLUSIONS: This is the first report on the combined association of CYP1A1 and SULT gene polymorphisms in endometrial cancer that suggests a decreased single nucleotide polymorphism of CYP1A1 and an increased single nucleotide polymorphism for SULT1A1 and SULT1E1 genes may be risk factors for endometrial cancer in Caucasians.     

Sulfotransferase 1A1 (SULT1A1) polymorphism and bladder cancer risk: a case-control study

Sulfotransferases (SULT) catalyze both the bioactivation and detoxification of a wide range of promutagens and procarcinogens. SULT1A1 appears to be an important phenol SULT because of its abundance and distribution in many tissues and wide substrate specificity. The SULT1A1 gene possesses a G-->A polymorphism that results in an Arg to His amino acid substitution, and the His(213) allele has been shown to have low activity and low thermal stability. Because of its functional role and published data showing the influence of Arg213His polymorphism on the risk of some cancers, we hypothesized that the His(213) allele of the SULT1A1 gene may modify bladder cancer risk. To test this hypothesis, we determined the SULT1A1 Arg213His genotypes in 384 incident bladder cancer patients and 386 healthy frequency-matched controls. A comprehensive epidemiologic interview was conducted on all participants to collect personal information, such as demographics and smoking status. The Arg/His and His/His genotypes were more common in the controls than the cases (P=0.035), resulting in a His(213) allele frequency of 35.0% in controls and 28.8% in cases. When individuals with the His(213) allele genotypes (Arg/His+His/His) were combined and compared to individuals with the Arg/Arg genotype, we observed a statistically significant reduced risk of bladder cancer (OR=0.72; 95% CI 0.54-0.97). When we examined the data by gender, there was a statistically significant reduced risk of bladder cancer only in women (OR=0.42; 95% CI 0.23-0.78) and not in men (OR=0.84; 95% CI 0.60-1.19) with the His(213) genotypes. In addition, there was a reduced bladder cancer risk in never smokers (OR=0.59; 95% CI 0.36-0.98) with the His(213) allele genotypes, but not in former (OR=0.82; 95% CI 0.54-1.25) or current smokers (OR=0.68; 95% CI 0.29-1.58). The His(213) allele genotypes also appeared to provide some protective benefit for current and former smokers, as compared to those with the Arg/Arg genotype. In conclusion, this study provides epidemiologic evidence of a reduced bladder cancer risk associated with the SULT1A1 His(213) polymorphism. Further studies are warranted to elucidate the function of this SULT1A1 polymorphism with regard to organ specificity, gene-environment interactions, and the gender-related difference we observed.     

Role of UGT1A1*28 and UGT1A1*6 for irinotecan-induced adverse drug reaction

Irinotecan is widely used in the treatment of colorectal, gastric, and lung cancers. However, adverse drug reactions such as severe diarrhea and neutropenia limit the dose of this drug. Irinotecan is metabolized by carboxylesterase to form an active metabolite, 7-ethyl-10-hydroxycamptothecin(SN-38), which in turn is subsequently conjugated by UGT-glucuronosyltransferase 1A1(UGT1A1)to yield an inactive form, SN-38 glucuronide(SN-38 G). The UGT1A1 gene polymorphisms contribute to the individual variation in adverse events among patients administered irinotecan. However, the distribution of polymorphisms shows large interethnic differences. The distribution of UGT1A1*28 greatly differs between Caucasians and Japanese; the frequency of UGT1A1*28 is high in Caucasians, whereas it is low in Asians including Japanese. Recently, it has been demonstrated that genetic variants of UGT1A1*6 in addition to UGT1A1*28 are associated with the occurrence of adverse events in irinotecan chemotherapy in Asians. This review summarizes recent studies to outline the role of UGT1A1*28 and UGT1A1*6 for irinotecan-induced adverse drug reaction in Japanese cancer patients.