生物节律调控关键基因遗传变异与乳腺癌患病风险的相关性

Association of genetic variantions of circadian clock genes and risk of breast cancer

目的研究生物节律调控关键基因Clock和Per2的遗传变异与乳腺癌发病风险的关系。方法采用病例一对照研究，使用TaqMan荧光定量PCR法检测406例乳腺癌患者和412例健康对照者位于Clock基因（~2070062）和Per2基因（rs2304672、rs2304669、rs934945）的4个位点的基因多“态性，采用非条件~gistic回归模型分析不同基因型或等位基因与乳腺癌发病风险的关系。结果携带rs2304669-TT基因型者发生乳腺癌的风险是携带rs2304669一CC＋CT基因型者的2．33倍（P=0．001）。单体型分析的结果也显示，所有含有rs2304669-T等位基因的单体型均可增加乳腺癌的发病风险。而另外3个位点未发现与乳腺癌的发病相关。结论位于Per2基因上的rs2304669位点可能与乳腺癌的发病风险相关；生物节律调控关键基因Per2的遗传变异会增加乳腺癌的发病风险，可能可以作为乳腺癌易感性的重要分子生物标志物。

Objective To investigate the relationship between genetic variantions of circadian clock genes and risk of breast cancer. Methods A case-control study including 406 breast cancer patients and 412 controls was conducted and genes Clock （rs2070062） and Per2 （ rs2304672, rs2304669, rs934945 ） were genotyped by TaqMan real-time PCR. Unconditional logistic regression model was used to analyze the association between the genetic polymorphisms and breast cancer. Results Individuals with the rs2304669- TT genotype showed significantly increased breast cancer risk with the OR of 2.33 when compared with the individuals with rs2304669-CC and CT genotypes （P = 0.001 ）. In addition, the three haplotypes containing the risk T allele of rs2304669 were identified to be associated with increased breast cancer risk. However, it was found that rs2304672, rs2070062 and rs934945 polymorphisms were not related with breast cancer risk. Conclusions The locus rs2304669 on Per2 gene is associated with breast cancer risk. Genetic variation of circadian clock genes may increase the susceptibility to breast cancer. Therefore, it may become an important biomarker of susceptibility to breast cancer.