Guo Hui, Chen Wei, Ming Jie, Zhong Rong, Yi Pengfei, Zhu Beibei, Miao Xiaoping, Huang Tao
Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Tumour Biol. 2015 Jul;36(7):5299-304. doi: 10.1007/s13277-015-3190-z. Epub 2015 Feb 14.
Cdc27, as a core component of anaphase-promoting complex (APC), is a cell cycle regulator, which participates in control of mitotic checkpoint and surveys the mitotic spindle to maintain chromosomal integrity. It was hypothesized that polymorphisms in cdc27 gene might contribute to the susceptibility of breast cancer (BC) through influencing the mitotic progression of cells. Therefore, a hospital-based case-control study with 463 BC patients and 536 controls was implemented to investigate the association of six single-nucleotide polymorphisms (SNPs) in cdc27 and BC risk in a Chinese Han population. Among the six SNPs, two SNPs of rs11570443 and rs12601027 were positively correlated with BC risk. Individuals carrying rs11570443-CT or CC genotypes showed a higher BC risk with the OR of 1.75 (95 % confidence interval (CI) = 1.13-1.69), compared with those carrying rs11570443-TT genotype. For rs12601027, an increased BC risk was significantly associated with homozygote TT genotype (odds ratio (OR) = 1.49, 95 % CI = 1.12-1.98) compared with homozygote CC and heterozygote CT genotypes. In addition, a significant interaction effect of these two SNPs was found. The rs12601027-TT in combination with rs11570443-CT/CC genotypes showed a strongly elevated risk of BC compared with rs12601027-CC/CT and rs11570443-TT genotype (OR = 1.95, 95 % CI = 1.06-3.59). These findings suggested that polymorphisms in cdc27 may contribute to the susceptibility of BC though functional studies are needed to further elucidate the underling mechanisms of the associations.
Cdc27作为后期促进复合物（APC）的核心成分，是一种细胞周期调节因子，参与有丝分裂检查点的控制并监测有丝分裂纺锤体以维持染色体完整性。据推测，cdc27基因的多态性可能通过影响细胞的有丝分裂进程而导致乳腺癌（BC）易感性增加。因此，开展了一项基于医院的病例对照研究，纳入463例BC患者和536例对照，以调查中国汉族人群中cdc27基因的6个单核苷酸多态性（SNP）与BC风险的关联。在这6个SNP中，rs11570443和rs12601027这两个SNP与BC风险呈正相关。与携带rs11570443 - TT基因型的个体相比，携带rs11570443 - CT或CC基因型的个体患BC的风险更高，比值比（OR）为1.75（95%置信区间（CI）= 1.13 - 1.69）。对于rs12601027，与纯合子CC和杂合子CT基因型相比，纯合子TT基因型与BC风险增加显著相关（比值比（OR）= 1.49，95% CI = 1.12 - 1.98）。此外，发现这两个SNP存在显著的交互作用。与rs12601027 - CC/CT和rs11570443 - TT基因型相比，rs12601027 - TT与rs11570443 - CT/CC基因型组合显示患BC的风险大幅升高（OR = 1.95，95% CI = 1.06 - 3.59）。这些发现表明，cdc27基因多态性可能导致BC易感性增加，不过仍需进行功能研究以进一步阐明这些关联的潜在机制。
