Yang Xiao-Yun, Yu Hai, Xi Ming-Rong, Yang Kai-Xuan, Pan Xiao-Ling, Hu Ming, Peng Zhi-Lan
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Int J Gynecol Cancer. 2009 May;19(4):585-90. doi: 10.1111/IGC.0b013e3181a39d03.
ARLTS1 has been identified in chromosome 13q14 as a tumor suppressor gene of the adenosine diphosphate-ribosylation factor family with pro-apoptotic characteristics. The ARLTS1 mutation Trp149Stop and Cys148Arg have been shown to be associated with familial cancers, but limited information is available regarding the impact of ARLTS1 variants on familial ovarian cancer (OC). The aim of this study was to evaluate the ARLTS1 genetic variants associated with familial OC risk in China. We genotyped 85 OC patients with family ovarian/breast history, 80 sporadic OC patients, and 120 controls from general population by denaturing high-performance liquid chromatography screening analysis followed by direct sequencing of the conspicuous polymerase chain reaction products. ARLTS1 Cys148Arg revealed a significant association with an increased risk of familial OC compared with both sporadic cases and controls in a dose-dependent manner (P = 0.0031 and 0.012, respectively). In the clinical-pathological study, our results support previous data in demonstrating that familial OC was associated with younger age at diagnosis (49.7 years vs 53.3 years; P = 0.014), higher proportion of tumors of advanced stages (81.2% vs 67.5%; P = 0.033), and higher rates of serous adenocarcinomas (76.4% vs 53.8%; P = 0.028) compared with sporadic OC cases. To investigate the association between genetic variants of ARLTS1 and the clinical-pathological characteristics of familial OC, we identified a significantly higher proportion of serous adenocarcinoma (55/67, 82.1%) and higher rates of advanced stage tumors (88.1% vs 55.6%; P = 0.004) in ARLTS1 Cys148Arg carriers. We showed a significantly increased risk of familial OC for ARLTS1 Cys148Arg variant, which indicate that ARLTS1 may play a role in familial OC.
ARLTS1在13号染色体q14区域被鉴定为一种具有促凋亡特征的二磷酸腺苷核糖基化因子家族的肿瘤抑制基因。ARLTS1突变Trp149Stop和Cys148Arg已被证明与家族性癌症相关，但关于ARLTS1变异对家族性卵巢癌（OC）影响的信息有限。本研究的目的是评估与中国家族性OC风险相关的ARLTS1基因变异。我们通过变性高效液相色谱筛选分析，随后对显著的聚合酶链反应产物进行直接测序，对85例有家族性卵巢/乳腺癌病史的OC患者、80例散发性OC患者以及120例来自普通人群的对照进行基因分型。与散发性病例和对照相比，ARLTS1 Cys148Arg以剂量依赖方式显示出与家族性OC风险增加显著相关（分别为P = 0.0031和0.012）。在临床病理研究中，我们的结果支持先前的数据，表明家族性OC与诊断时年龄较轻（49.7岁对53.3岁；P = 0.014）、晚期肿瘤比例较高（81.2%对67.5%；P = 0.033）以及浆液性腺癌发生率较高（76.4%对53.8%；P = 0.028）相关，与散发性OC病例相比。为了研究ARLTS1基因变异与家族性OC临床病理特征之间的关联，我们在ARLTS1 Cys148Arg携带者中发现浆液性腺癌比例显著更高（55/67，82.1%）以及晚期肿瘤发生率更高（88.1%对55.6%；P = 0.004）。我们显示ARLTS1 Cys148Arg变异使家族性OC风险显著增加，这表明ARLTS1可能在家族性OC中起作用。
