PALLD基因rs1071738位点单核苷酸多态性与乳腺癌的相关性研究

The association of single nucleotide polymorphism at rs 1071738 locus of PALLD gene with breast cancer

目的探讨含钯蛋白(palladin,PALLD)基因rs1071738位点单核苷酸多态性(SNP)与乳腺癌发生风险以及进展的相关性.方法所有受试者取5ml静脉血,分离血浆后提取总RNA,采用反转录实时定量PCR(RT-PCR)检测miR-96和miR-182水平,使用Sanger测序法检测白细胞PALLD基因rs1071738位点基因型.结果PALLD基因rs1071738位点C等位基因是乳腺癌的保护因素(OR=0.200,95%CI:0.104~0.379,P<0.001).PALLD基因rs1071738位点突变型乳腺癌患者中Ⅲ/Ⅳ期乳腺癌的数量少于Ⅰ/Ⅱ期(OR=0.114,95%CI:0.005~0.904,P=0.015).乳腺癌患者血浆中miR-96和miR-182水平显著低于对照组,且Ⅰ、Ⅱ期患者血浆miR-96和miR-182水平显著高于Ⅲ、Ⅳ期患者,野生型患者血浆miR-96和miR-182水平显著低于突变型,差异均有统计学意义(P<0.05).结论PALLD基因rs1071738位点单核苷酸多态性与乳腺癌发生风险和进展情况相关,其机制可能是PALLD基因rs1071738位点SNP影响血浆miR-96和miR-182水平.

Objective To study the correlation between the palladium(PALLD)gene rs1071738 single nucleotide polymorphism(SNP) and breast cancer. Method Five milliliters venous blood sample were collected from every cases and total RNAs were extracted from the plasma. MiR-96 and miR-12 were detected by reverse transcription real-time quantitative PCR(RT-PCR). Leukocyte cells PALLD rs1071738 locus genotype were detected by Sanger sequencing. Results The C allele of the PALLD gene rs1071738 locus was a protective factor for breast cancer(OR=0.200, 95% CI:0.104~0.379,P<0.001). The numbers of stage Ⅲ/Ⅳ breast cancer in PALLD gene rs1071738-mutants were less than that of stage Ⅰ/Ⅱ(OR=0.114,95%CI:0.005~0.904,P=0.015). The levels of miR-96 and miR-182 in plasma of breast cancer patients were significantly lower than those in the control group,the levels of plasma miR-96 and miR-182 in patients with stage Ⅰ and Ⅱ were significantly higher than those in stage Ⅲ and Ⅳ,the levels of plasma miR-96 and miR-182 in wild-type patients were significantly lower than those in the mutants(P<0.05). Conclusion The PALLD gene rs1071738 single nucleotide polymorphism is associated with the risk and progression of breast cancer,the mechanism may be that the PALLD rs1071738 locus SNP affects plasma miR-96 and miR-182 levels.