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目的研究CYP19A1基因R264C的(C→T)单核苷酸多态性基因型在上海地区BRCA1/BR-CA2基因突变阴性的遗传倾向乳腺癌人群中的分布及其与乳腺癌发病风险的相关性。方法对114例无BRCA1/2突变的家族性/早发性乳腺癌患者和121名正常对照者进行CYP19A1基因第7外显子的聚合酶链反应扩增,随后进行DNA直接测序鉴定其R264C的单核苷酸多态性基因型,比较基因型分布和发病风险的关系;危险度比值比(oddratio,OR)及95%可信区间(confidenceinterval,CI)应用非条件Logistic回归分析计算。结果CYP19A1基因R264C多态的CC、CT、TT基因型在病例组中的分布频率分别为84(77.8%),22(20.4%),2(1.8%);在对照组的分布频率分别为87(77.7%),24(21·4%),1(0.9%);在研究的总人群中,CT基因型的频率为20.9%(46/220),TT基因型的频率为1.4%(3/220)。以CC基因型为参照,CT或TT基因型没有显著性地提高乳腺癌的发病危险,其中携带CT基因型风险为(OR=1.16,95%CI:0.53~2.55),携带TT基因型风险为(OR=1.44,95%CI:0.12~17.15);经过月经状态和身体质量指数分层,也未能发现其与乳腺癌发病的相关性。结论CYP19A1基因R264C的单核苷酸多态性在中国汉族人群中的分布有别于其他种族,有其自身的分布特点;R264C可能与上海地区中国汉族人群乳腺癌发生的遗传易感性无关,尚不足作为低外显率的乳腺癌易感基因位点,不建议作为未来临床基因筛查的候选指标。
Objective To investigate the distribution of CYP19A1 R264C (C → T) single nucleotide polymorphism (SNP) genotypes in genetic predisposition breast cancer patients with negative BRCA1 / BR-CA2 mutations in Shanghai and their association with the risk of breast cancer . Methods A total of 114 patients with familial / early-onset breast cancer without BRCA1 / 2 mutation and 121 normal control subjects were enrolled in the polymerase chain reaction amplification of exon7 of CYP19A1 gene, and then DNA sequencing was performed to identify the R264C Single nucleotide polymorphism (SNP) genotypes were compared between the genotypes and the risk of developing the disease. Odds ratios (odds ratios) and 95% confidence intervals (CI) were calculated using non-conditional logistic regression analysis. Results The frequencies of genotypes CC, CT and TT of R264C polymorphism of CYP19A1 gene were 84 (77.8%), 22 (20.4%) and 2 (1.8%) respectively in the case group. The frequency of distribution in the control group was 87 (19.7%), 24 (21.4%), and 1 (0.9%). Of the total study population, the frequency of CT genotype was 20.9% (46/220), TT genotype frequency was 1.4% (3 / 220). CT genotype as a reference, CT or TT genotype did not significantly increase the risk of breast cancer risk, which carries CT genotype risk (OR = 1.16,95% CI: 0.53 ~ 2.55), carrying TT genotype risk (OR = 1.44, 95% CI: 0.12-17.15). After the menstrual state and body mass index were stratified, their correlation with the incidence of breast cancer was also not found. Conclusion The single nucleotide polymorphism of CYP19A1 R264C in Chinese Han population is different from other races and has its own distribution characteristics. R264C may not be related to the genetic susceptibility to breast cancer in Chinese Han population in Shanghai area. Insufficient as low penetrance of breast cancer susceptibility loci, is not recommended as a candidate for future clinical gene screening.