CYP19A1基因rs7176005单核苷酸多态性与乳腺癌发病风险及临床病理特征的关系

Association of CYP19A1 gene rs7176005 single nucleotide polymorphism with breast cancer risk and clinicopathologic features of tumor

目的 了解CYP19A1基因rs7176005单核苷酸多态性与乳腺癌发生及临床病理特征的关系。方法 研究对象来自四川大学华西医院2012年9月至2016年11月乳腺科患者或者体检人员，分为乳腺癌病例组、乳腺良性疾病组和对照组，其中乳腺癌病例组共138例，即术后常规石蜡切片确诊为原发性乳腺癌患者；乳腺良性疾病组共293例，即同时期门诊彩超提示为乳腺实性包块，经穿刺诊断为纤维腺瘤或者腺病的患者，按年龄±5岁与乳腺癌病例组匹配；对照组共259名，即同期门诊体检的健康女性，未发现乳腺相关疾病，按年龄±5岁与乳腺癌病例组匹配。采用直接测序法分析研究对象CYP19A1基因rs7176005单核苷酸的多态性，采用Hardy-Weinberg检验分析3组基因型的遗传平衡性，采用χ2检验分别比较3组间rs7176005位点基因型的分布差异以及携带不同基因型乳腺癌病例组对象间临床病理特征的差异。结果 乳腺癌病例组、乳腺良性疾病组和对照组研究对象年龄分别为（44.69±8.09）、（42.33±11.44）和（41.92±9.61）岁。Hardy-Weinberg遗传平衡定律检验结果显示，乳腺癌病例组、乳腺良性疾病组和对照组对象等位基因C和T的构成比差异均无统计学意义（χ2值分别为0.83、0.34、0.04，P值分别为0.363、0.561、0.852），即3组对象均符合遗传平衡，具有衡定性及群体代表性。138例乳腺癌病例中，CYP19A1基因rs7176005位点不同基因型的患者肿瘤大小分布差异有统计学意义（χ2=10.66，P=0.031），其中，携带TT和CT基因型的患者肿瘤大小以≤2 cm为主，比例分别为12/16和58%（40例），而携带TT基因型者以〉2且≤5 cm为主，比例为51%（27例）；不同基因型患者间临床分期的分布差异有统计学意义（χ2=11.19，P=0.025），携带CC和CT基因型者以Ⅱ期为主，比例分别为45.3%（24例）和52.2%（36例），携带TT基因型者以Ⅰ期为主，比例为9/16。结论 CYP19A1基因rs7176005单核苷酸多态性与乳腺癌发病无相关性，但含C等位基因的乳腺癌患者肿瘤增殖较快，发病时肿瘤也较大。

Objective The aim of this study was to investigate the association of the CYP19A1 rs7176005 single nucleotide polymorphism （SNP） with breast cancer risk and with clinicopathologic features of tumors.Methods This study was conducted by including 138 patients with breast cancer （cancer group）, those who diagnosed as primary breast cancer after operation by pathology. There were 293 cases in the group of benign breast disease which was presented as a solid mass by the color ultrasound and pathologically diagnosed as ＂fibroadenoma or adenosis＂ （benign breast disease group）, the cases were paired with breast cancer patients by age±5 in the same period, and there were 259 cases in the group of healthy control who received routine physical examination during the same period and were paired with breast cancer patients by age±5 without any detection of breast related diseases （healthy control group） at West China hospital between September 2012 and November 2016. The CYP19A1 rs7176005 SNP was detected by a direct sequencing method. Hardy-Weinberg test was used to analyze the genetic balance of the 3 groups. Chi square test was used to compare the distribution of rs7176005 genotypes between the 3 groups, and the differences of clinicopathological features in breast cancer patients carrying different genotypes.Results The ages of the breast cancer cases, the benign breast disease group and the healthy control group were （44.69±8.09）, （42.33±11.44） and （41.92±9.61） years old, respectively. Hardy-Weinberg equilibrium test identified that the composition ratios of alleles C and T in breast cancer group, benign breast disease group and healthy group were not statistically significant （χ2 values were 0.83, 0.34 and 0.04, respectively, P values were 0.363, 0.561, and 0.852, respectively）. All the three groups met the genetic balance, had consistency and could represent the population. Among the 138 cases of breast cancer, the CYP19A1 rs7176005 SNP was significantly associated with the diameter of the tumor （P=0.031）. The majority of tumor size was 〈2 cm in patients who carrying TT and CT genotypes, and the proportion was 75% （12/16） and 58% （40/69）, respectively. While those patients with TT genotype were mainly 〉2 cm and ≤5 cm, and the proportion was 51% （27/53）. The distribution of TNM stage among patients with different genotypes was also statistically significant （χ2=11.19, P=0.025）. The most common stage was Ⅱ in Patients who carrying CC and CT genotypes, and the proportion was 45.3% （24/53） and 52.2% （36/69）, respectively. While those patients with TT genotype was mainly in stage Ⅰ and the proportion was 56.3% （9/16）.Conclusion Though the CYP19A1 rs7176005 SNP is not associated with breast cancer development, breast cancer patients with the C allele exhibit a high tumor growth rate and large diameters.