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Jianfeng Xu,
Zengnan Mo,
Dingwei Ye,
Meilin Wang,
Fang Liu,
Guangfu Jin,
Chuanliang Xu,
Xiang Wang,
Qiang Shao,
Zhiwen Chen, [......],
Xiao-Ou Shu,
Wei Zheng,
Hongbing Shen,
Li Jin,
Rong Shi,
Daru Lu,
Xuejun Zhang,
Jielin Sun,
S Lilly Zheng,
Yinghao Sun
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ABSTRACT: Prostate cancer risk-associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk-associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10(-14)) and 19q13.4 (rs103294, P = 5.34 × 10(-16)) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10(-4)). These findings may advance the understanding of genetic susceptibility to prostate cancer.
Nature Genetics 09/2012; · 35.53 Impact Factor
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Xiaoling Lin,
Lianxi Qu,
Zhuo Chen,
Chuanliang Xu,
Dingwei Ye,
Qiang Shao,
Xiang Wang,
Jun Qi,
Zhiwen Chen,
Fangjian Zhou, [......],
Rong Na,
Qiang Ding,
Daru Lu,
Rong Shi,
Jielin Sun,
Fang Liu,
S Lilly Zheng,
Zengnan Mo,
Yinghao Sun,
Jianfeng Xu
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ABSTRACT: BACKGROUND: A rare mutation G84E in HOXB13 was recently identified to be associated with prostate cancer (PCa) in Caucasians. The goal of this study is to test association between HOXB13 genetic variants and PCa risk in Chinese men. METHODS: All study subjects were part of the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). In the first stage, we screened for mutations by sequencing the HOXB13 coding region in 96 unrelated PCa patients. In stage 2, G84E and novel mutations found in stage 1 were genotyped in 671 PCa patients and 1,536 controls. In stage 3, mutation status in 751 additional PCa patients was imputed via haplotype. RESULTS: The G84E mutation was not detected in this study. However, a novel mutation, G135E, was identified among 96 patients in stage 1. It was also observed twice in 575 additional PCa patients but not in 1,536 control subjects of stage 2. The frequency of G135E was significantly different between cases and controls, with a P-value of 0.027, based on Fisher's exact test. Haplotype estimation showed that G135E mutation carriers shared a unique haplotype that was not observed in other subjects. In stage 3, two more PCa patients were predicted to carry the G135E mutation. CONCLUSIONS: We identified a novel rare mutation in the HOXB13 gene, G135E, which appears to be a founder mutation. This mutation is associated with increased PCa risk in Chinese men. Consistent with a previous report, our findings provide further evidence that rare mutations in HOXB13 contribute to PCa risk. Prostate © 2012 Wiley Periodicals, Inc.
The Prostate 06/2012; · 3.48 Impact Factor
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ABSTRACT: The biological significance of tripartite motif (TRIM) proteins is increasingly being appreciated due to their roles in a broad range of biological processes that associated with innate immunity. In this study, we have described the structural and functional analysis of TRIM3a from zebrafish. Annotation of domain architectures found that the TRIM3a fulfills the TRIM-NHL rule of domain composition with a Filamin/ABP280 domain and NHL repeats at its C-terminal region. In addition, the mRNA expression level of TRIM3a was the highest in brain, and with a relatively higher level in spleen, liver, and gill. A strong expression starting at 36 h post fertilization (hpf) was observed by real-time PCR and could be detected in brain by in situ hybridization, suggesting that TRIM3a protein might play an important role in brain development in zebrafish. Considering that TRIM3a has a RING finger domain, we expressed and purified the TRIM3a protein and performed ubiquitylation assays, our results showed that TRIM3a underwent self-polyubiquitylation in combination with E1, UbcH5c, biotin-ubiquitin in vitro. Meanwhile, TRIM3a-R without the RING domain was expressed and purified as well, in vitro ubiquitylation assays showed that the self-ubiquitylation of TRIM3a was dependent on its RING domain, suggesting that TRIM3a might function as a RING finger E3 ubiquitin ligase.
Fish & Shellfish Immunology 01/2012; 32(5):621-8. · 3.32 Impact Factor
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Meilin Wang,
Fang Liu,
Ann W Hsing,
Xiang Wang,
Qiang Shao,
Jun Qi,
Yu Ye,
Zhong Wang,
Hongyan Chen,
Xin Gao, [......],
Sha Tao,
Guangfu Jin,
Jielin Sun,
Daru Lu,
S Lilly Zheng,
Yinghao Sun,
Zengnan Mo,
Changjun Yin,
Zhengdong Zhang,
Jianfeng Xu
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ABSTRACT: A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case-control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 × 10(-8) for rs12653946 at 5p15, 4.43 × 10(-5) for rs339331 at 6q22 and 8.42 × 10(-4) for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (P(trend) = 2.58 × 10(-13)), and men with 5-6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0-2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78-2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men.
Carcinogenesis 11/2011; 33(2):356-60. · 5.70 Impact Factor
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Jie Zheng,
Fang Liu,
Xiaoling Lin,
Xiang Wang,
Qiang Ding,
Haowen Jiang,
Hongyan Chen,
Daru Lu,
Guangfu Jin,
Ann W Hsing, [......],
Meilin Wang,
Zhengdong Zhang,
Yanlin Hu,
Jielin Sun,
S Lilly Zheng,
Xu Gao,
Chuanliang Xu,
Zengnan Mo,
Yinghao Sun,
Jianfeng Xu
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ABSTRACT: Genome-wide association studies (GWAS) have identified more than 30 single nucleotide polymorphisms (SNPs) that were reproducibly associated with prostate cancer (PCa) risk in populations of European descent. In aggregate, these variants have shown potential to predict risk for PCa in European men. However, their utility for PCa risk prediction in Chinese men is unknown.
We selected 33 PCa risk-related SNPs that were originally identified in populations of European descent. Genetic scores were estimated for subjects in a Chinese case-control study (1,108 cases and 1,525 controls) based on these SNPs. To assess the performance of the genetic score on its ability to predict risk for PCa, we calculated area under the curve (AUC) of the receiver operating characteristic (ROC) in combination with 10-fold cross-validation.
The genetic score was significantly higher for cases than controls (P = 5.91 × 10(-20)), and was significantly associated with risk of PCa in a dose-dependent manner (P for trend: 4.78 × 10(-18)). The AUC of the genetic score was 0.604 for risk prediction of PCa in Chinese men. When ORs derived from this Chinese study population were used to calculate genetic score, the AUCs were 0.631 for all 33 SNPs and 0.617 when using only the 11 significant SNPs.
Our results indicate that genetic variants related to PCa risk may be useful for risk prediction in Chinese men. Prospective studies are warranted to further evaluate these findings.
The Prostate 07/2011; 72(5):577-83. · 3.48 Impact Factor
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Fang Liu,
Ann W Hsing,
Xiang Wang,
Qiang Shao,
Jun Qi,
Yu Ye,
Zhong Wang,
Hongyan Chen,
Xin Gao, Guozeng Wang, [......],
Ling Guo,
Xiaoling Lin,
Sha Tao,
Guangfu Jin,
Jielin Sun,
Daru Lu,
S Lilly Zheng,
Yinghao Sun,
Zengnan Mo,
Jianfeng Xu
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ABSTRACT: More than 30 prostate cancer (PCa) risk-associated loci have been identified in populations of European descent by genome-wide association studies. We hypothesized that a subset of these loci might be associated with PCa risk in Chinese men. To test this hypothesis, 33 single nucleotide polymorphisms (SNP), one each from the 33 independent PCa risk-associated loci reported in populations of European descent, were investigated for their associations with PCa risk in a case-control study of Chinese men (1108 cases and 1525 controls). We found that 11 of the 33 SNP were significantly associated with PCa risk in Chinese men (P < 0.05). The reported risk alleles were associated with increased risk for PCa, with allelic odds ratios ranging from 1.12 to 1.44. The most significant locus was located on 8q24 region 2 (rs16901979, P = 5.14 × 10(-9)) with a genome-wide significance (P < (-8) ), and three loci reached the Bonferroni correction significance level (P < 1.52 × 10(-3)), including 8q24 region 1 (rs1447295, P = 7.04 × 10(-6)), 8q24 region 5 (rs10086908, P = 9.24 × 10(-4)) and 8p21 (rs1512268, P = 9.39 × 10(-4)). Our results suggest that a subset of the PCa risk-associated SNP discovered by genome-wide association studies among men of European descent is also associated with PCa risk in Chinese men. This finding provides evidence of ethnic differences and similarity in genetic susceptibility to PCa. Genome-wide association studies in Chinese men are needed to identify Chinese-specific PCa risk-associated SNP.
Cancer Science 07/2011; 102(10):1916-20. · 3.33 Impact Factor
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ABSTRACT: Alkaline-encrusted cystitis (AEC) has been reported sporadically during the past 90 years. It occurs mainly in immunocompromised or debilitated patients after urologic procedures. However, we report two unexpected cases of AEC in patients who were young and not under conditions of transplantation, immunocompromise or debilitation. Both had undergone a ureteroscopic lithotripsy procedure before being diagnosed as having encrusted cystitis. Although no information on such atypical patients is available, at least to our knowledge, we undertook a further report and discussion on the imaging characteristics of this atypical AEC.
Urologia Internationalis 01/2010; 85(3):364-7. · 0.99 Impact Factor
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ABSTRACT: The lack of effective anti-tumor therapy for renal cell carcinoma (RCC) has stimulated the search for novel target whose inhibition could block tumorigenesis. Recently, reduced DLC-1 has been shown to be associated with aggressive and highly metastatic renal cell carcinoma. In this study, the biological role of DLC-1 on cell growth, migration and cell cycle progression in RCC cells was investigated. Over-expression of DLC-1 was associated with a marked inhibition of cell growth (P<0.01). The inhibitory effect was partly due to the induction of apoptosis and cell cycle arrest in G(0)/G(1) accompanied by up-regulation of the intracellular signal proteins of p27 and down-regulation of cyclin D1 and cyclin E. Furthermore, DLC-1 induced FAK dephosphorylation of focal adhesion proteins inhibited cell migration (P<0.05). Decreased DLC-1 expression strongly correlated with proliferative activity, as indicated by the elevated levels of Ki67. Restoration of DLC-1 expression in RCC cells led to Bcl-2 and caspase-3 mediated apoptosis as well as attenuated the ability of the cells to form RCC tumors in athymic nude mice (P<0.05). Taken together, these results suggest that DLC-1 plays a crucial role in signal transduction pathway regulating the cell proliferation, migration, and carcinogenesis of human RCC.
Cancer letters 05/2009; 283(1):59-67. · 4.86 Impact Factor
