摘要目的 探讨纤溶酶原激活物抑制因子1 (plasminogen activator inhibitor 1,PAI-1)基因的单核苷酸多态性(SNP)与中国汉族女性乳腺癌的易感性及预后的关联性.方法 选取HapM印数据库中,中国北京汉族人群PAId基因的标签SNP(tSNP)位点;使用TaqMan探针即时荧光定量PCR方法,在1 160例乳腺浸润性导管癌患者和1 318名正常对照中进行基因分型实验;根据tSNP分型及其连锁不平衡程度,推算出每位个体的单体型和双体型;采用多种统计学方法,分析tSNP、单体型和双体型与乳腺癌的易感性及预后的关联性.结果 在PAI-1与乳腺癌易感性的关联分析中,我们发现rs6090(G＞A) AA基因型携带者与GG或GA基因型携带者相比,发生乳腺癌的风险提高3.79倍(OR=4.79,95％ CI=1.O1 ～22.64,P=0.048 0);rs2227672(G＞T) TT基因型携带者与GG或GT基因型携带者相比,发生乳腺癌的风险提高1.52倍(OR =2.52,95％ CI=1.26～5.01,P=0.008 6).在PAI-1与乳腺癌患者无进展生存期的关联分析中,rs2227692(C＞T) CT基因型携带者与CC基因型携带者相比,术后乳腺癌复发、转移或患者死亡的风险降低46％(HR =0.54,95％ CI=0.30～0.97,P=0.0404);在身体质量指数＜23的患者中,rs2227631(G＞A) AA基因型携带者与GG或GA基因型携带者相比,术后发生复发、转移或死亡的风险提高3.99倍(HR=4.99,95％ CI=1.66～15.02,P=0.004 2);在HER2阳性患者中,rs2227667(G＞A) AA基因型携带者与GG或GA基因型携带者相比,术后发生复发、转移或死亡的风险提高2.98倍(HR=3.98,95％ CI=1.47～10.80,P=0.0067);在肿瘤直径＞2 cm的患者中,rs2227692(C＞T) CT或TT基因型携带者与CC基因型携带者相比,术后发生复发、转移或死亡的风险降低51％(HR=0.49,95％ CI=0.27～0.88,P=0.017 0).结论 PAI-1的单核苷酸多态性可以影响中国汉族女性乳腺癌的易感性及预后.这些结果若能够在其他中国汉族人群中得以验证,将为乳腺癌的个体化风险评估及预后评估提供分子遗传标志物.

abstractsObjective To study the effects of single nucleotide polymorphisms (SNP) in Plasminogen activator inhibitor 1 (PAI-1) on breast cancer susceptibility and patients' prognosis among a Chinese Han women population.Methods Six tag SNP (tSNP) of PAI-1 were selected according to HapMap CHB population,and TaqMan realtime PCR method was used to genotype the 6 tSNP in 1 160 breast cancer cases and 1 318 age-matched controls among Chinese Han women.Haplotypes and diplotypes were inferred according to genotyping data and linkage disequilibrium.Finally,the associations of tSNP,haplotypes and diphypes with breast cancer susceptibility and patients' prognosis were analyzed.Results Regarding to breast cancer susceptibility,for rs6090 (G ＞ A),AA genotype carriers had 3.79 times higher risk of develoPing breast cancer (OR =4.79,95％ CI =1.01-22.64,P =0.048 0) than GG or GA genotype carriers.For rs2227672 (G ＞ T),TT genotype carriers had 1.52 times higher breast cancer risk than GG or GT genotype carriers (OR =2.52,95％ CI =1.26-5.01,P =0.008 6).Regarding to breast cancer prognosis,women who carried rs2227692 (C ＞ T) CT genotype had 46％ lower risk of developing recurrence,metastasis or death than CC genotype carriers (HR =0.54,95％ CI =0.30-0.97,P =0.040 4).Using stratified association analysis,among BMI ＜ 23 patients,those women who carried AA genotype of rs2227631 (G ＞ A) had 3.99 times higher risk of developing the events (recurrence,metastasis or death) than GG or GA genotype carriers (HR =4.99,95％ CI =1.66-15.02,P =0.004 2).Among HER2 positive patients,those women who carried AA genotype of rs2227667 (G ＞ A) had 2.98 times higher risk of developing the events (recurrence,metastasis or death) than GG or GA genotype carriers (HR =3.98,95％ CI =1.47-10.80,P =0.006 7).Among patients with tumors ＞ 2 cm,those women who carried rs2227692 (C ＞ T) CT or TT genotype had 51％ lower risk of developing the events (recurrence,metastasis or death) than CC genotype carriers (HR =0.49,95％ CI =0.27-0.88,P =0.017 0).Conclusions The study indicates that single nucleotide polymorphisms in PAI-1 may affect breast cancer susceptibility and survival in Chinese Han women.The study may contribute to individualized evaluation of breast cancer risk and patients' prognosis if these data are validated in some other Chinese Han populations.