CRY1基因单核苷酸多态性与乳腺癌风险的关联研究

摘要

Background and purpose: Cryptochrome-1 (CRY1) gene is a main part of the negative feedback loop in circadian clock gene family, which was first discovered in plants. Recently much attention has been paid to polymorphisms of circadian clock gene family and breast cancer susceptibility at home and abroad. The study aimed to investigate the associations between single nucleotide polymorphism of CRY1 gene and susceptibility of breast cancer in Chinese population. Methods: Genotyping was performed using TaqMan method in 1 523 histological-confirmed breast cancer cases and 1 599 healthy controls. Results: The genotype distributions of CRY1 polymorphisms were significantly different between cases and controls (X2=6.394, P=0.041). Multivariate logistic regression analysis showed that the carriers of the GT genotype had a significantly decreased risk of breast cancer (adjusted OR=0.743, 95％CI: 0.580-0.951), the individual who carried G variant (GT/GG) had a decreased risk of breast cancer by 23.2％ (adjusted OR=0.768, 95％CI: 0.606-0.971). Stratified analysis showed that the protective effect of carrying G variant (GT/GG) was more evident in subjects with postmenopausal status, menarche age older than 13, first pregnancy age older than 25, abortion frequency less than 2, history of benign disease, without family history of cancer. Conclusion: The CRY1 rs1056560 T＞G polymorphism is associated with a significantly decreased risk of breast cancer. More rigorous laboratory studies of ethnically diverse population and functional studies are warranted to confirm our findings.%背景与目的:隐花色素-1(cryptochrome-1,CRY1)基因属于生物钟基因家族,它最早在植物体内发现,是生物钟基因负反馈环的主要部分.近年来生物钟基因多态性与乳腺癌易感性的关系引起国内外研究者的广泛关注,本研究探讨生物钟基因CRY1的单核苷酸多态性与乳腺癌易感性的关系.方法:采用TaqMan 单核苷酸多态性分型技术检测1 523例中国汉族女性乳腺癌患者和1 599名正常女性对照者CRY1基因rs1056560位点的基因型,采用SPSS 16.0软件进行数据处理.结果:CRY1基因rs1056560位点三种基因型(TT/GT/GG)在乳腺癌患者和对照间的分布差异具有显著性(x2=6.394,P=0.041),与TT基因型相比,GT基因型可以显著降低乳腺癌的发病风险(OR=0.743,95%CI:0.580～0.951),携带至少一个G等位基因(GT/GG)的个体乳腺癌风险降低23.2%(OR=0.768,95%CI:0.606～0.971).分层分析后发现,rs1056560 T＞G保护作用在绝经后妇女、初潮≥13岁、初孕≥25岁、无肿瘤家族史者、无乳腺良性病史及流产0～1次妇女中尤为显著.结论:CRY1基因rs1056560 T＞G单核苷酸多态性与中国人群乳腺癌的发病风险相关,这一结论有待于不同种族人群的关联研究以及功能学研究的进一步证实.