CLOCK基因单核苷酸多态性与乳腺癌易感性的病例对照研究

目的：探讨生物钟CLOCK基因的单核苷酸多态性与乳腺癌易感性的关系。方法：采用应用聚合酶链式反应-限制性片断长度多态性（PCR-RFLP）技术检测1 499例中国汉族女性乳腺癌患者和1 592例正常女性对照者CLOCK基因rs3805151位点的基因型，采用SPSS 16.0软件进行数据处理。结果：CLOCK基因CC型、CT型和TT型在病例组和对照组间的分布差异有统计学意义（χ2=9.712，P=0.008），与CC型相比，杂合型CT可以显著增加乳腺癌的发病风险 （OR=1.41，95% CI：1.07～1.87），携带T等位基因（CT/TT）的个体乳腺癌风险增加35%（OR=1.35，95% CI：1.04～1.76）。分层分析显示，携带T等位基因绝经后、无肿瘤家族史者、无乳腺良性病史的个体患乳腺癌风险增加。结论：CLOCK基因rs3805151 C>T可增加乳腺癌发病风险，这一结论有待于进一步通过不同种族人群的关联研究以及功能学研究的证实。

Genetic Polymorphisms in CLOCK and Increased Risk of Breast Cancer: A Case Control Study

Genetic Polymorphisms in CLOCK and Increased Risk of Breast Cancer: A Case Control StudyXiaoling ZHU, Hongji DAI, Mingli CAO, Hong ZHENG, Yanrui ZHAO, Fengju SONG, Kexin CHENCorrespondence to: Kexin CHEN, E-mail: chenkexin1963@yahoo.comDepartment of Epidemiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, ChinaThis work was supported by the National Natural Science Foundation of Chia (No. 30771844)Abstract Objective: To investigate the relationship between single nucleotide polymorphisms in the CLOCK gene andsusceptibility to breast cancer in a Chinese population. Methods: Genotyping was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) in 1,499 histologically confirmed breast cancer cases and 1,592 healthycontrols. SPSS16.0 was used for data processing. Results: There were significant differences in genotype distribution of CLOCKpolymorphisms between the breast cancer cases and controls ( χ2= 9.712, P = 0.008 ). Multivariate logistic regression analysis showedthat the carriers of the CT genotype had an increased risk of breast cancer ( adjusted OR = 1.41, 95% CI = 1.07-1.87 ), an individualwho carried the T variant ( CT/TT ) had a 35% increased risk of breast cancer ( adjusted OR = 1.35, 95% CI = 1.04-1.76 ). Stratifiedanalysis indicated that the negative effect of T variant ( CT/TT ) was more evident in postmenopausal subjects who had no history ofbenign disease or cancer. Conclusions: CLOCK ( rs3805151, C > T ) polymorphisms were associated with an increased risk of breastcancer. Further studies on people of different ethnicities and functional studies are expected to confirm these findings.Keywords Breast cancer; CLOCK gene; Single nucleotide polymorphism; Genetic susceptibility; Risk factors