ABCB1基因多态性与乳腺癌患者化疗所致严重中性粒细胞减少症的相关性研究

Association between ABCB1 Gene Polymorphisms and Chemotherapy-induced Severe Neutropenia in Patients with Breast Cancer

目的:探讨乳腺癌患者三磷酸腺苷结合盒转运子B亚家族成员1(ABCB1)基因多态性与多柔比星和环磷酰胺(AC)联合化疗所致严重中性粒细胞减少症的相关性。方法:选择我院2012-2015年接受AC联合化疗的乳腺癌患者218例,采用聚合酶链-限制性片段长度多态性分析法进行ABCB1 2677G>T/A、3435C>T基因多态性检测,考察患者不同年龄、体质量指数、临床分期、基因型等各因素与AC联合化疗所致严重中性粒细胞减少症的相关性,并采用多元逻辑回归分析中性粒细胞减少症的危险因素。结果:218例乳腺癌患者中,罹患严重中性粒细胞减少症的共170例,占78.0%。ABCB1 2677G>T/A基因多态性中,GT或GA基因型,TT、TA或AA基因型及GG基因型在严重中性粒细胞减少症中的分布频率分别为80.6%、86.2%、60.0%,差异有统计学意义(P<0.05);ABCB1 3435C>T基因多态性中,TT、CT及CC基因型在严重中性粒细胞减少症中的分布频率分别为86.4%、78.4%、72.7%,差异无统计学意义(P>0.05)。患者的天冬氨酸转氨酶水平及ABCB1 2677G>T/A基因多态性均与严重中性粒细胞减少症相关(P<0.05),且ABCB1 2677G>T/A基因多态性是中性粒细胞减少症的危险因素[比值比=3.875,95%置信区间(1.555,9.922),P=0.008]。结论:ABCB1 2677G>T/A基因多态性可能与乳腺癌患者AC联合化疗所致严重中性粒细胞减少症风险增加有关。

OBJECTIVE： To discuss the association between ABCB1 gene polymorphisms and adriamycin and cyclophospha- mide （AC） combined with chemotherapy-induced severe neutropenia in patients with breast cancer. METHODS： 218 breast cancer patients receiving AC combined with chemotherapy were selected from our hospital during 2012-2015; PCR-RFLP was used to de- tect polymorphisms ofABCB1 2677G〉T/A and 3435C〉T. The associated between different age, BMI, clinical stages genotypes, etc and AC combined with chemotherapy-induced severe neutropenia were investigated, and risk factors of neutropenia were ana- lyzed by multivariate logistic regression. RESULTS： Among 218 breast cancer patients, 170 patients suffered from severe neutrope- nia, accounting for 78.0%. Among ABCB1 2677G〉T/A polymorphisms, distribution frequency of GT or GA genotype, TT, TA or AA genotype, GG genotype in severe neutropenia were 80.6%, 86.2% and 60.0%, with statistical significance （P〈0.05）. Among ABCB1 3435C〉T polymorphisms, distribution frequency of TT, CT and CC genotype in severe neutropenia were 86.4%, 78.4% and 72.7%, there was no statistical significance （P〉0.05）. AST and ABCB1 2677G〉T/A polymorphisms were correlated with severe neutropenia （P〈0.05）, and ABCB1 2677G〉T/A polymorphism was a strong predictor of neutropenia [OR=3.875, 95 % CI （1.555,9.922）, P=0.008]. CONCLUSIONS： ABCB 1 2677 〉 T/A polymorphisms may be aggravate AC combined with che- motherapy-induced neutropenia in patients with breast cancer.