[Association of Single Nucleotide Polymorphisms in PAI-1 with Breast Cancer Susceptibility and Prognosis].

OBJECTIVE 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 dipltypes 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.