CYP24A1基因多态性与绝经后女性乳腺癌的易感性研究

Study on the association between CYP24A1 genetic polymorphisms and risks related to postmenopausal breast cancer

目的探究CYP24A1基因多态性与绝经后女性乳腺癌风险关联。方法采用以人群为基础的病例对照研究方法,在江苏省无锡市选取绝经后女性1134人(589例乳腺癌患者和545例非乳腺癌患者)。采取Sequenom MassARRAY平台对CYP24A1单核苷酸多态性位点(rs2209314、rs2585428、rs2762941、rs3787555、rs4909959、rs912505和rs927650)进行分型,通过logistic回归分析CYP24A1多态性与乳腺癌的易感性,并采用广义多因子降维方法分析位点-位点之间的交互作用。结果CYP24A1基因的rs2209314、rs2585428、rs2762941、rs3787555、rs4909959、rs912505和rs927650在共显性、显性、隐性和相加模型下均未发现与乳腺癌存在统计学关联。在腰围<80 cm的人群中,rs2585428能降低乳腺癌风险(OR=0.64,95%CI:0.42~0.96),rs3787555也表现出相似关联(OR=0.58,95%CI:0.38~0.87)。同时rs2585428、rs3787555和rs4909959与腰围在乳腺癌发病风险存在交互作用。rs2209314、rs3787555和rs912505之间可能存在位点-位点之间的交互作用(P=0.0547)。结论在绝经后人群中,rs2585428和rs3787555与乳腺癌的易感性存在关联。

Objective To evaluate the associations between CYP24A1 genetic polymorphisms and related risks on breast cancer among postmenopausal women.Methods We carried out a population-based case-control study to include 1134 postmenopausal women(589 cases and 545 controls)from Wuxi,Jiangsu province and to explore the association between CYP24A1 polymorphisms and related risks on breast cancer.Seven CYP24A1 variants(rs2209314,rs2585428,rs2762941,rs3787555,rs4909959,rs912505 and rs927650)were genotyped by Sequenom MassARRAY platform.Logistic regression method was used to estimate the CYP24A1 genetic variants and susceptibility of breast cancer.Loci-loci interactions were evaluated by a generalized multifactor dimensionality reduction(GMDR)method.Results Result showed that rs2209314,rs2585428,rs2762941,rs3787555,rs4909959,rs912505 and rs927650 of CYP24A1 were not associated with breast cancer under the codominant,dominant,recessive or additive models.Among the population with<80 cm waist circumstance,rs2585428 was associated with the reduced risks on breast cancer(OR=0.64,95%CI:0.42-0.96).Similar negative association was observed for rs3787555(OR=0.58,95%CI:0.38-0.87).The genotypes of rs2585428,rs3787555 and rs4909959 showed significant interactions with waist circumstance on the risk of breast cancer.Also,rs2209314,rs3787555 and rs912505 in CYP24A1 could alter the risk of breast cancer by way of loci-loci interaction.Conclusion CYP24A1 variants rs2585428 and rs3787555 were associated with risks of susceptibility on breast cancer,among postmenopausal women.