RT Journal Article
SR Electronic
T1 Association of the ARLTS1 Variants With Familial Ovarian Cancer Risk in China
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 585-590
OP 585-590
DO 10.1111/IGC.0b013e3181a39d03
VO 19
IS 4
A1 Yang, Xiao-Yun
A1 Yu, Hai
A1 Xi, Ming-Rong
A1 Yang, Kai-Xuan
A1 Pan, Xiao-Ling
A1 Hu, Ming
A1 Peng, Zhi-Lan
YR 2009
UL http://ijgc.bmj.com/content/19/4/585-590.abstract
AB 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.