CYP17基因多态性与天津汉族女性散发乳腺癌风险关系的研究

Association between a Genetic Polymorphism in CYP17 and Sporadic Breast Cancer Risk in Tianjin Women of Han Nationality

  • 摘要: 目的: 探讨CYP17基因多态性与乳腺癌发生危险性的关系。 方法: 用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法,对299例乳腺癌患者和242例正常人的CYP17基因MspA1I多态位点进行检测,确定出CYP17基因的3种基因型,即野生型A1/A1、杂合型A1/A2、突变型A2/A2。非条件logistic回归分析计算各种基因型的乳腺癌发病风险(OR及调整OR值)及其95%可信区间(95%CI)。 结果: CYP17A1A1、A1A2和A2A2三种基因型分布频率,乳腺癌患者组中分别为15.7%、56.3%和28.1%,对照组中分别为18.2%、51.7%和30.2%;乳腺癌患者组A1、A2等位基因频率分别为43.8%,56.2%,对照组为44%,56%。CYP17基因型及等位基因型在两组间分布频率的差别均无统计学意义(P>0.05)。基因型A1/A2与A1/A1比较、A2/A2与A1/A1比较OR值分别为0.80(95%CI0.50-1.27)、0.93(95%CI0.55-1.56)。分层分析显示携带等位基因A2的绝经后妇女如果初孕年龄≥25岁,可增加乳腺癌的发病风险(OR2.41,95%CI1.04-5.62)。多因素分析显示:初潮年龄早(<13岁),初孕年龄晚(≥25岁),末孕年龄晚(≥30岁),良性乳腺疾病史均是乳腺癌的发病危险因素。 结论: 整体上CYP17MspA1I多态位点3种基因型的分布与乳腺癌发病风险无关,但发现初孕年龄≥25岁的携带CYP17A2等位基因型的绝经后妇女易患乳腺癌。

     

    Abstract: Objective: To investigate the relationship between the CYP17 5'-untranslated region MspA1I polymorphism and the incidence of breast cancer. Methods: Risk factors and CYP17 genotyping data were obtained from a Chinese popula-tion-based case-control study including 299 cases of breast cancer and 242 normal controls. The MspA1I polymorphism was detected using the PCR-restriction fragment length polymorphism (PCR-RFLP) assay, and the genotypes identified were labeled homozygous wild type(A1A1), heterozygous variant(A1A2), or homozygous variant(A2A2). Crude and adjusted odds ratios (OR) were evaluated and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses. Results: In breast cancer cases, the prevalence rates of CYP17 genotype A1A1, A1A2, and A2A2 were 15.7%,56.2%, and 28.1%, respectively. In the control group, the prevalence rates of CYP17 genotype A1A1, A1A2, and A2A2 were 18.2%, 51.7%, and 30.2%,respectively. The frequencies of CYP17 A1 and A2 alleles were 43.8% and 56.2% in breast cancer patients, respectively, and 44% and 56% in the control group, respectively. No significant difference was found in the genotype distributions or allele frequencies of CYP17 polymorphism between the two groups (P>0.05). CYP17 A1A2 and A2A2 genotypes were not associated with breast cancer, with odds ratios(ORs) of 0.80(95% CI 0.50-1.27) and 0.93(95% CI 0.55-1.56). Stratified analysis showed that the postmenopausal cases with allele A2 were more likely to have had their first pregnancy at a later age(OR 2.413, 95% CI 1.035-5.623). Multivariate analysis showed that early menarche (<13years), later age during the first pregnancy( ≥25years) or last pregnancy(≥30years), and history of benign breast dis-ease were the risk factors for breast cancer. Conclusion: The presence of the MspA1I polymorphism in the CYP17 gene's 5'-UTR may not be a risk factor for breast cancer. Individuals with allele A2 who have their first pregnancy at a later age (≥25years) have a higher risk of developing breast cancer.

     

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