乳腺癌发病风险及侵袭特性与白细胞介素-8和CXCR2基因多态性的关系

Association between genetic polymorphism of interleukin-8 and CXCR2 with risk and aggressive forms of breast cancer

目的探讨细胞因子白细胞介素（IL）-8（-251）位点及其受体CXCR2（＋1208）位点多态性与乳腺癌发病风险及侵袭特性的关系。方法采用等位基因特异-聚合酶链反应（AS—PCR）分析方法检测228名乳腺癌患者和1（30例健康对照者的IL-8（-251）位点及其受体CXCR2（＋1208）位点多态性分布，并进行统计学分析。结果IL-8（-251）位点TA型和AA型以及CXCR2（＋1208）TT型是乳腺癌的高危基因型[比值比（OR）=1．57，95％可信区间（C1）=1．08—2．32；OR=2．68，95％CI=1．26～2．99；OR=2．02，95％CI：1．08～3．62]，在两组间表达频率的差异有统计学意义（P〈0．05）。携带1个及以上高危基因型增加患乳腺癌的风险。分层分析表明携带IL-8（-251）等位基因A和CXCR2（＋1208）等位基因T增加乳腺癌的侵袭特性，其分布频率在肿瘤的高组织学分级（OR=1．95，P〈0．01；OR=1．52，P〈0．05）和淋巴结转移阳性（OR=1．65，P〈0．05；OR=1．66，P〈0．01）中差异有统计学意义。另外，IL-8（-251）A等位基因与ER（-）乳腺癌显著相关（OR=1．65，P〈0．05）。结论IL-8和CXCR2的基因多态性可能与女性乳腺癌的发生发展关系密切．可作为乳腺癌早期基因诊断的指标。

Objective To explore the association between interleukin （IL）-8 gene -251 A/T and CXCR2 gene ＋ 1208 C/T polymorphisms with the risk and aggressive forms of breast cancer. Methods Totally 228 breast cancer patients and 100 non-cancer female controls were selected. The genotypes were detected by using AS-PCR method. Results IL-8 （ - 251 ） TA/AA and CXCR2 （ ＋ 1208 ） TT were the high risk genotypes （ OR = 1.57, 95% CI - 1.08-2. 32 ; OR = 2. 68, 95% CI = 1.26-2. 99 ; OR = 2. 02, 95% CI = 1.08-3.62）, and there was significant difference in the expression distributation between the case group and the control group. The risk of breast carcinoma was significantly in the patients carrying one high-risk genotype and above7. The stratified analysis indicated that IL-8 （ - 251 ） A allele and CXCR2 （ ＋ 1208 ） T allele are highly associated with aggressive forms of breast cancer as denied by high grade and lymph node metastases （ OR = 1.65, 95% CI = 1.21-2. 74 ; OR = 1.66, 95% CI = 1.17-2. 73 ）. Conclu- sion The results indicated that the polymorphisms in IL-8 and CXCR2 genes, which might be associated with breast cancer risk of Chinese women, as well as disease progress, could be used as an indicator of the early genetic diagnosis of breast cancer.