Association of genetic polymorphisms in AURKA, BRCA1, CCNE1 and CDK2 with the risk of endometrial carcinoma and clinicopathological parameters among Chinese Han women

作者：Zheng, Li-Yuan; Song, Ai-Ping; Chen, Lan; Liu, Dong-Ge; Li, Xiang-Hong; Guo, Hong-Yon; Tian, Xin-Xia^*; Fang, Wei-Gang

来源：European Journal of Obstetrics & Gynecology and Reproductive Biology, 2015, 184: 65-72.

DOI：10.1016/j.ejogrb.2014.11.001

• Single nucleotide polymorphism (SNP)
• Endometrial carcinoma
• AURKA
• BRCA1
• CCNE1

Objective: Centrosome aberrations and cell-cycle deregulations have important implications for the development of endometrial carcinoma. AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation. This study aimed to investigate whether genetic polymorphisms in these four genes may contribute to endometrial carcinoma susceptibility and progression in Chinese Han women.
Study design: : A total of twenty-two single nucleotide polymorphisms (SNPs) were selected according to the public HapMap database (HapMap Data Release #27; Chinese Beijing population), and genotyped using TaqMan Realtime PCR method in 530 endometrial adenocarcinoma cases and 825 age-matched controls from Chinese Han women. Then, haplotype blocks were reconstructed according to our genotyping data.
Results: For AURKA, the rs911162 was associated with increased risk of endometrial carcinoma [in co-dominant model: adjusted odds ratio (aOR) = 4.92, 95% CI = 1.24-19.55, P = 0.0235]. The haplotype GA (rs6064391 + rs911162) in block 1 of AURKA was also associated with increased risk of endometrial carcinoma (aOR = 1.25, 95% CI = 1.07-2.06, P = 0.0189). For BRCA1, the minor allele homozygotes of rs8067269 could decrease the risk of endometrial carcinoma (in co-dominant models: aOR = 0.52, 95% CI = 0.34-0.80, P = 0.0032), so was the haplotype CTCAG (rs8176323 + rs8176199 + rs3737559 + rs8067269 + rs2070833) (aOR = 0.69, 95% CI = 0.50-0.95, P = 0.0234). Moreover, we found several associations between genetic variations in CCNE1, BRCA1 and AURKA and clinicopathological parameters.
Conclusions: This study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may contribute to endometrial carcinoma susceptibility or progression in Chinese Han women.

• 出版日期2015-1
• 单位北京市肿瘤防治研究所; 北京医院; 北京大学