CYP1B1基因多态性与卵巢癌易感性的研究

目的:研究CYP1B1基因外显子2密码子119(G-T)、外显子3密码子432(C-G)多态性与卵巢癌遗传易感性的关系。方法:应用等位基因特异性聚合酶链反应(AS-PCR)法对53例卵巢癌患者和30例对照者进行CYP1B1基因密码子119(G-T)、密码子432(C-G)突变分析,用免疫组化SP法进一步研究雌激素受体(ER)、孕激素受体(PR)的表达,分析其是否受CYP1B1基因多态性的影响。结果:CYP1B1基因密码子432中等位基因C、G在卵巢癌组和对照组分布的差异有统计学意义(P<0.05),其中等位基因G使卵巢癌发病风险增加2.71倍。CYP1B1基因密码子432C/G各基因型分布两组间差异有统计学意义(P<0.01),纯合突变(G/G)基因型、杂合突变(C/G)基因型与野生(C/C)基因型相比,患卵巢癌的危险度分别提高了4.53倍和4.43倍。此外,432G/G、C/G基因型者ER阳性表达率高于432(C/C)基因型,三者间有显著差异(P<0.05)。结论:CYP1B1基因密码子432突变等位基因与卵巢癌的发生有一定关系,突变基因型增加了卵巢癌的发病风险,且与ER的表达相关。

Association between gene polymorphism of CYP1B1 and susceptibility to ovarian cancer

Objective:To study the association between gene polymorphisms of cytochrome P450 1B1(CYP1B1) in exon 2 codon 119(G-T),exon 3 codon 432(C-G) and the susceptibility to ovarian cancer.Methods:Allele-specific polymerase chain reaction method was used to analyze gene polymorphisms in exon 2 codon 119(G-T),exon 3 codon 432(C-G) of CYP1B1 in 53 cases of ovarian cancer and 30 cases of normal control.Immunohistochemistry method(SP) was used to investigate whether the expression of estrogen receptor-α(ERα) and progesterone receptor(PR) were influenced by the CYP1B1 genotypes in ovarian cancer.Results:The frequency of allele C,G on codon 432C/G of CYP1B1 gene showed a significant difference between the ovarian cancer group and the control group(P<0.05),with an odds of 2.79.There was a significant difference in the frequency of genotype C/C,C/G and G/G between the two groups(P<0.01).Compared with wild-type C/C,the susceptibility of ovarian cancer with the genotypes of homozygotic mutation G/G and heterozygote mutation C/G was increased by 4.53 and 4.43-fold,respectively.Moreover,the positive expression of ER in genotype G/G and C/G was significant higher than that in genotype C/C(χ~2=6.167,P<0.05).Conclusion:The gene polymorphisms of CYP1B1 in exon 3 codon 432 may be a genetic susceptibility factor for ovarian cancer.The mutation of CYP1B1 gene increases the risk of ovarian cancer,and has positive correlation with ER expression.