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ABSTRACT: It has been demonstrated that single nucleotide polymorphisms (SNPs) of SIPA1 (signal-induced proliferation associated gene 1) are associated with metastatic efficiency in both human and rodents. The purpose of this study was to determine whether SIPA1 545 C > T polymorphism was associated with overall survival in patients with metastatic breast cancer. In this study, SIPA1 545 C > T polymorphism was detected in 185 metastatic breast cancer patients using polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Survival curves for patients with SIPA1 545 C > T polymorphism was compared using the Kaplan-Meier method with log-rank tests. We found that SIPA1 545 C > T polymorphism was significantly associated with survival in 185 patients with metastatic breast cancer. Patients with SIPA1 545 T/T genotype had a significantly worse overall survival (OS) than did patients with C/T or C/C genotype (50.0% vs. 62.9%, P = 0.042). Moreover, in multivariate analysis, as compared with the C/C or C/T genotype, the T/T genotype remained an independent unfavorable prognostic marker of OS in this cohort (hazard ratio [HR] = 2.16; 95% CI = 1.12-4.15; P = 0.022). Our findings indicate that metastatic breast cancer patients with SIPA1 545 T/T genotype have a poorer survival compared to patients with C/C or C/T genotype.
Frontiers of medicine. 01/2013;
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ABSTRACT: Recent studies suggested that breast cancer patients who carry a BRCA1 germline mutation benefit from poly (ADP-ribose) polymerase (PARP) inhibitors; therefore, it would be of great interest to detect BRCA1 somatic mutations in sporadic breast cancers. In this study, we detected BRCA1 somatic mutations in tumor cDNA from 144 Chinese women with sporadic breast cancer by using polymerase chain reaction (PCR)-direct sequencing assay. In total, eight BRCA1 alterations (three nonsense mutations and five missense mutations) were identified in this cohort of 144 sporadic breast cancers. We further confirmed that 5 out of 144(3.5%) sporadic breast cancer cases carried a BRCA1 somatic mutation, including two novel nonsense mutations (c.191_212del22 and c.2963C>G) resulting in a truncated protein and three missense mutations (c.114G>T, c.925A>C, and c.824G>A). The two cases with BRCA1 somatic truncating mutations also contained a TP53 somatic mutation in the tumors. Our study suggested that a small subset of sporadic breast cancers do harbor BRCA1 somatic mutations; these patients who carry a BRCA1 somatic mutation may be potential candidates for treatment with PARP inhibitors.
Breast Cancer Research and Treatment 11/2011; 132(1):335-40. · 4.43 Impact Factor
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ABSTRACT: Although there are some studies to investigate germline mutations in BRCA1/2 genes in Chinese women with familial breast cancer, many of them suffer relatively small sample size. In this study, we screened germline mutations in BRCA1/2 genes in a cohort of 409 Chinese women with familial breast cancer from north China by using a PCR-sequencing assay. A total of 43 deleterious mutations in BRCA1/2 genes were identified in this cohort, including 17 novel mutations and 6 recurrent mutations. The frequencies of BRCA1 and BRCA2 mutations were 3.9% (16/409) and 6.6% (27/409), respectively; the mutation rate of BRCA2 was 1.7-fold higher than that of BRCA1. The entire mutation rate of BRCA1/2 was 10.5% in this cohort; however, the mutation rate of BRCA1/2 genes was 23.0% in 78 familial breast cancer patients whose tumors were diagnosed at or before the age of 40. The mean age at diagnosis of breast cancer in BRCA1 carriers (42.8 years) and BRCA2 carriers (45.1 years) was younger than non-carriers (51.0 years) in this cohort (P = 0.005; P = 0.01, respectively). In addition, both BRCA1 carriers and BRCA2 carriers were more likely to exhibit triple-negative breast cancer (ER-, PgR-, and HER2-) than non-carriers (BRCA1 carriers vs. non-carriers, 69.2 vs. 23.0%, P = 0.001; BRCA2 carriers vs. non-carriers, 45.8 vs. 23.0%, P = 0.01). Our study suggested that the spectrum and characteristics of BRCA1/2 mutations in Chinese familial breast cancer exhibit some unique features, and Chinese women with familial breast cancer whose tumors are diagnosed at or before the age of 40 are good candidates for BRCA1/2 testing.
Breast Cancer Research and Treatment 05/2011; 132(2):421-8. · 4.43 Impact Factor
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Yin Liu,
Ji Liao,
Ye Xu,
Weiqiu Chen,
Dongyun Liu,
Tao Ouyang,
Jinfeng Li,
Tianfeng Wang, Zhaoqing Fan,
Tie Fan,
Benyao Lin,
Xingzhi Xu,
Yuntao Xie
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ABSTRACT: The association between the CHEK2 and breast cancer risk in Chinese women is unknown. Here, we screened the full CHEK2 coding sequence in 118 Chinese familial breast cancer cases who are negative for mutations in BRCA1 and BRCA2, one recurrent mutation, CHEK2 c.1111C>T (p.H371Y), was identified in five index cases in this cohort. Functional analysis suggested that CHEK2 p.H371Y was a pathogenic mutation that resulted in decreased kinase activity. We further screened the CHEK2 p.H371Y mutation in 909 unselected breast cancer cases and 1,228 healthy individuals. The frequencies of the CHEK2 p.H371Y in familial and unselected breast cancer cases and controls were 4.24% (5/118), 1.76% (16/909), and 0.73% (9/1228), respectively. The p.H371Y mutation was significantly associated with increased breast cancer risk in unselected breast cancer (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.07-5.52, P = 0.034). Our results indicate that the recurrent mutation, p.H371Y, confers a moderate risk of breast cancer in Chinese women. Hum Mutat 32:1-4, 2011. © 2011 Wiley-Liss, Inc.
Human Mutation 05/2011; · 5.69 Impact Factor
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Breast Cancer Research and Treatment 05/2011; 129(3):1019-20. · 4.43 Impact Factor
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Liang Shi,
Bin Dong,
Zhongwu Li,
Yunwei Lu,
Tao Ouyang,
Jinfeng Li,
Tianfeng Wang, Zhaoqing Fan,
Tie Fan,
Benyao Lin,
Zhaoyi Wang,
Yuntao Xie
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ABSTRACT: PURPOSE Recently, a 36-kDa variant of estrogen receptor alpha (ER-alpha66), ER-alpha36, has been identified and cloned. ER-alpha36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated "nongenomic" signaling pathway. Here, we investigate the association between ER-alpha36 expression and tamoxifen resistance in patients with breast cancer. PATIENTS AND METHODS ER-alpha36 protein expression in tumors from 896 women (two independent cohorts, 1 and 2) with operable primary breast cancer was assessed using an immunohistochemistry assay. Results In the first cohort of 710 consecutive patients, overexpression of ER-alpha36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-alpha66-positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-alpha36 was not associated with survival in patients with ER-alpha66-positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-alpha66-negative tumors whether they received tamoxifen (n = 73) or not (n = 149). In the second cohort of 186 patients who only received tamoxifen as adjuvant therapy, overexpression of ER-alpha36 was significantly associated with poorer DFS and DSS in 156 ER-alpha66-positive patients from this cohort, and ER-alpha36 remained an independent unfavorable factor for both DFS and DSS in these 156 patients by a multivariate analysis (DFS: hazard ratio [HR] = 5.47; 95% CI, 1.81 to 16.51; P =. 003; DSS: HR = 13.97; 95% CI, 1.58 to 123.53; P = .018). CONCLUSION Women with ER-alpha66-positive tumors that also express high levels of ER-alpha36 are less likely to benefit from tamoxifen treatment.
Journal of Clinical Oncology 07/2009; 27(21):3423-9. · 18.37 Impact Factor
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Ye Xu,
Lihua Yao,
Ailian Zhao,
Tao Ouyang,
Jinfeng Li,
Tianfeng Wang, Zhaoqing Fan,
Tie Fan,
Benyao Lin,
Youyong Lu,
Yuntao Xie
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ABSTRACT: In vitro studies suggest that p53 codon 72 genotype alters the apoptotic capacity of p53 protein, with the 72 arginine (R) form of wild-type p53 harboring a greater apoptosis-inducing potential than the 72 proline (P) variant. The aim of this study was to investigate whether the association between the p53 codon 72 genotype and breast cancer survival was modified by p53 gene status. In our study, we examined the p53 codon 72 genotype and p53 mutations (through exons 4-9) in paraffin-embedded specimens from 414 breast cancer patients with a median follow-up of 8.2 years. We report that the p53 codon 72 genotype was significantly associated with disease-free survival (DFS, p = 0.02) but not with disease-specific survival (DSS, p = 0.24) in the entire study population (n = 414). In contrast, the codon 72 genotype was strongly associated with both DFS (p = 0.001) and DSS (p = 0.04) among patients with a wild-type p53 tumor (n = 346), patients with the P/P variant had worse DFS and DSS than did those with the P/R or R/R variant in this subgroup of patients. More importantly, as compared with the P/R or R/R variant, the P/P variant remained an independent prognostic factor of DFS among patients with a wild-type p53 tumor (HR = 2.5; 95%CI = 1.4-4.4; p = 0.003). We conclude that the effect of p53 codon 72 genotype on breast cancer survival is dependent on p53 gene status, the P/P variant is strongly associated with poor prognosis among patients with a wild-type p53 tumor.
International Journal of Cancer 07/2008; 122(12):2761-6. · 5.44 Impact Factor
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Weiqiu Chen,
Kaifeng Pan,
Tao Ouyang,
Jinfeng Li,
Tianfeng Wang, Zhaoqing Fan,
Tie Fan,
Benyao Lin,
Youyong Lu,
Weicheng You,
Yuntao Xie
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ABSTRACT: The data related to BRCA1 germline mutation in Chinese women with familial breast cancer is increasing. However, little is known the frequency of BRCA1 mutations in Chinese women with familial or early-onset breast cancer from Northern China, and few studies are available to investigate the clinicopathological characteristics of BRCA1 tumors in Chinese women. In this study, we detected germline mutations in BRCA1 in a cohort of 139 breast cancer patients who either have a family history of breast cancer (n = 68) or whose tumors are diagnosed at or before the age of 35 (n = 71) from Northern China. A total of 6 deleterious BRCA1 mutations were identified in this cohort, 4 of which (5587-1 del8, 3887 del AG, IVS21 + 1delG, and 2129 ins TG) are novel and one mutation (3478del5) detected in this study was only reported in Chinese population. The frequency of BRCA1 mutations in women with familial or early-onset breast cancer was 5.9% (4/68) or 2.8% (2/71) in this cohort, respectively; but the mutations were detected in 4 of 16(25.0%) familial breast cancer patients whose tumors were diagnosed before the age of 40. Moreover, BRCA1 mutation tumors tended to be high histological grade, and to be negative for ER, PgR, and Her-2 compared with tumors without BRCA1 mutations. Our study suggests that Chinese women with a family history of breast cancer whose tumors are diagnosed before age of 40 would be a suitable candidate for BRCA1 testing; and BRCA1 tumors in Chinese women exhibit an aggressive phenotype.
Breast Cancer Research and Treatment 06/2008; 117(1):55-60. · 4.43 Impact Factor
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Ye Xu,
Ying Sun，Lihua Yao,
Liang Shi,
Ying Wu,
Tao Ouyang,
Jinfeng Li,
Tianfeng Wang, Zhaoqing Fan,
Tie Fan,
Benyao Lin,
Luowen He,
Pingping Li,
Yuntao Xie
Annals of oncology. 01/2008;
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Hongxia Li,
Lihua Yao,
Tao Ouyang,
Jinfeng Li,
Tianfeng Wang, Zhaoqing Fan,
Tie Fan,
Bin Dong,
Benyao Lin,
Jiyou Li,
Yuntao Xie
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ABSTRACT: p73 gene shares structural and functional similarities to p53, and plays an important role in modulating cell-cycle arrest and apoptosis. A common non-coding polymorphism of exon 2 of the p73 gene (designated as GC/AT) may affect gene expression, thus, it may lead to functional significance. The correlation of this polymorphism with breast cancer survival has not been investigated. In this study, by using genomic DNA p73 GC/AT polymorphism was detected by PCR-SSCP in 526 breast cancer patients with a median follow-up of 7.3 years. Among the 526 breast cancer patients, 4% of the patients were homozygous for the AT/AT genotype, 39% were heterozygous GC/AT and 57% were homozygous for the GC/GC genotype. We found that patients with the GC/GC genotype had a significantly worse clinical outcome than did patients with the AT Variants (AT/AT or GC/AT genotype) (5-year disease-free survival, 74.2 versus 95.0 or 84.1%, P=0.02; 5-year overall survival, 78.9 versus 95.0 or 87.5%, P=0.01, respectively). As compared with the GC/AT and AT/AT genotypes, the GC/GC genotype remained an independent prognostic indicator of disease-free survival (HR 1.82, P=0.003) and overall survival (HR 1.99, P=0.004) in multivariate analysis. Our results suggest that the GC/GC genotype is significantly associated with poor prognosis in breast cancer and raise the possibility that analysis of p73 polymorphism may provide useful prognostic information for breast cancer patients. Additional independent studies are needed to confirm these findings.
Carcinogenesis 03/2007; 28(2):372-7. · 5.70 Impact Factor
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Ye Xu,
Lihua Yao,
Hongxia Li,
Tao Ouyang,
Jinfeng Li,
Tianfeng Wang, Zhaoqing Fan,
Benyao Lin,
Youyong Lu,
Olle Larsson,
Yuntao Xie
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ABSTRACT: Several studies have demonstrated that tumor cell-derived RNA is presented in the plasma from breast cancer patients. However, no studies have focused on the detection of plasma erbB2 mRNA in breast cancer. In this study the expression of erbB2 mRNA in the plasma was analyzed in 106 breast cancer patients and 50 healthy subjects by using a nested RT-PCR strategy, and the circulating tumor cells were also detected by using a nested RT-PCR for detection of mammaglobin transcripts in the peripheral blood. Plasma erbB2 mRNA was detectable in 46 (43.3%) breast cancer patients, whereas only 5 normal subjects (10%) were positive in the control group (p = 0.001). The presence of erbB2 mRNA in the plasma was not associated with menopausal status, erbB2 expression in primary tumor tissues, tumor size, histological grade, Ki-67 expression or lymph node involvement, but it exhibited a trend for correlation with increasing tumor stages (p = 0.085), and the presence of erbB2 mRNA in the plasma was significantly associated with negative estrogen receptor (ER) and progesterone receptor (PR) status of the primary tumors (p = 0.031 and 0.026, respectively). Furthermore, in a small subset of 36 breast cancer patients we found the presence of plasma erbB2 mRNA was significantly correlated with the occurrence of circulating tumor cells (p = 0.01). Our study suggests that breast cancer patients with the presence of erbB2 mRNA in the plasma may have a high malignancy or an aggressive phenotype, and frequently detecting plasma erbB2 mRNA may provide a novel approach for monitoring breast cancer progression or response to treatment.
Breast Cancer Research and Treatment 06/2006; 97(1):49-55. · 4.43 Impact Factor
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Hongxia Li,
Liya Feng,
Ye Xu,
Lihua Yao,
Tao Ouyang,
Jinfeng Li,
Tianfeng Wang, Zhaoqing Fan,
Benyao Lin,
Jiyou Li,
Yuntao Xie
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ABSTRACT: A relatively little is known of whether CYP2D6 *10 (188 C to T) polymorphism mediates susceptibility to breast cancer. In this study the CYP2D6 *10 polymorphism was detected in Chinese women (286 breast cancer patients and 305 healthy women) by a PCR-RFLP assay. We found that women with the 188T/T genotype displayed a slightly increased risk for breast cancer as compared with those with the 188C/C genotype (OR 1.36, CI 0.89-2.1), the association of the 188T/T genotype with breast cancer risk was more pronounced among postmenopausal women (OR 1.49, CI 0.8-2.76), but the association did not reach statistical significance. Furthermore, we found that patients carrying the 188T/T or T/C genotype were more likely to be a positive lymph node status than those with the 188C/C genotype (OR 2.12, CI 1.08-4.18, P = 0.019). Our results suggest that CYP2D6 *10 mutant 188T/T genotype displays a non-significant increased risk for breast cancer. Moreover, patients carrying 188T/T or T/C genotype might exhibit a more aggressive phenotype than those carrying 188C/C genotype, as the observation association of genotype with clinical outcome may be due to chance, therefore, further studies are required to confirm our present findings.
Acta Oncologica 02/2006; 45(5):597-601. · 3.33 Impact Factor
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ABSTRACT: Recent studies have highlighted that the p53 codon 72 polymorphism plays a crucial role in modulating wild-type p53 apoptotic capacity, and as such may influence the response to chemotherapy. Thus, the purpose of this study was to investigate whether the p53 codon 72 polymorphism might influence pathologic response to neoadjuvant chemotherapy in primary breast cancer.
One hundred and ten operable breast cancer patients received anthracycline-based neoadjuvant chemotherapy and p53 codon 72 polymorphism status was analyzed by PCR-RFLP.
The distribution of initial clinical stage, tumor size, estrogen receptor or progesterone receptor status, menopausal status, or erbB2 expression was not significantly different among the polymorphic variants. However, we found that only 13% (3 of 23) of patients with the Pro/Pro variant had a good pathologic response, defined as a complete pathologic response or minimal residual disease. In comparison, 40% (22 of 55) or 37.5% (12 of 32) of patients with the Pro/Arg or Arg/Arg variant had a good pathologic response (P = 0.019). Moreover, patients with the Pro/Pro variant were more likely to have a positive axillary lymph node status than those with the Pro/Arg or Arg/Arg variant (P = 0.007). Furthermore, in multivariate analysis, p53 codon 72 polymorphism was found to be a strong predictor of pathologic response (odds ratio 6.7, 95% confidence interval, 1.4-31.2; P = 0.016).
Our study indicates that breast cancer patients with the Pro/Pro variant may be less sensitive to anthracycline-based treatment than those with the Pro/Arg or Arg/Arg variant and suggests that analysis of p53 codon 72 polymorphism may provide a simple predictive marker for selecting the right breast cancer patients to anthracycline-based neoadjuvant chemotherapy in clinical setting.
Clinical Cancer Research 11/2005; 11(20):7328-33. · 7.74 Impact Factor
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ABSTRACT: This study was designed to (a) analyze the correlation between the expression of Cdx2 and Hep and the clinicopathologic features of patients with gastric carcinoma, and (b) determine the value of combined analysis of Cdx2 and Hep expression in distinguishing histologic types and prognoses of gastric carcinomas.
The expression of Cdx2 and Hep were studied using immunohistochemistry of paraffin-embedded tumor specimens from 109 patients who underwent D2 resection for gastric adenocarcinoma from 1995 to 1998.
Nuclear Cdx2 and Hep expression was detected in 36.7% (40 of 109) and 54.1% (59 of 109) of gastric carcinoma cases, respectively. Expression of Cdx2 and Hep was significantly higher in intestinal-type carcinomas than in diffuse-type carcinomas (P = 0.027 and P = 0.037, respectively). There was a clear negative correlation between Cdx2 expression and lymph node metastasis (P = 0.029), as well as between Hep expression and depth of wall invasion (P = 0.011). The patients with Cdx2-positive or Hep-positive expression shows higher survival rate than those with Cdx2-negative or Hep-negative expression (P = 0.0008 and P = 0.003, respectively). Multivariate analysis revealed that the expression of Cdx2 and Hep were independent prognostic indicators of gastric carcinoma. The combination of Cdx2 and Hep expression was significantly lower in diffuse-type carcinoma than in intestinal or mixed-type carcinoma. Multivariate analysis revealed that Cdx2 and Hep expression was an independent prognostic indicator of gastric carcinoma (P < 0.001).
These data suggest that combined analysis of Cdx2 and Hep has significant value in distinguishing histologic types and in predicting the prognosis of gastric carcinoma.
Clinical Cancer Research 10/2005; 11(17):6162-70. · 7.74 Impact Factor
