Validation of associations between ESR1 variants and breast cancer risk in Chinese cohorts.

Estrogen receptor-a (ER) protein plays a key role in breast carcinogenesis, and common genetic variants in the corresponding gene locus have been associated with breast cancer risk in different populations. Here, we analyzed estrogen receptor 1 (ESR1) associations in two hospital-based studies of patients from the south of China. Three single-nucleotide polymorphisms (SNPs; rs3757318, rs2046210, and rs3734805) in ESR1 were selected from previous genome-wide association study results and were genotyped using the Sequenom MassARRAY® iPLEX System in 845 breast cancer patients and 882 healthy controls. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Stratified analyses according to the status of ER and progesterone receptor (PR) were also performed. Of the three SNPs, rs3757318 did not pass the Hardy-Weinberg equilibrium test and was excluded from the subsequent analysis. The other two SNPs (rs2046210 and rs3734805) were strongly associated with susceptibility to breast cancer. Allele T of rs2046210 and allele C of rs3734805 were risk alleles and the adjusted ORs were 1.348 (95%CI = 1.172-1.550, P = 0.0001) and 1.319 (95%CI = 1.144-1.522, P = 0.0001), respectively. Furthermore, the risk allele of rs2046210 gave negative results for ER and PR expression in an immunohistochemical test, with ORs of 0.602 (95%CI = 0.384-0.944, P = 0.027) and 0.532 (95%CI = 0.338-0.837, P = 0.006), respectively. Our study further supports associations between rs2046210 and rs3734805 and breast cancer risk in Chinese women.

Effect of recombinant human endostatin on the expression of c-Myc and bFGF in mouse gastric cancer cells.

The aim of this study was to observe the effects of re-combinant human endostatin on the proliferation and apoptosis of mouse gastric cancer cells, and explore some possible mechanisms of recom-binant human endostatin inhibition of cancer. A murine gastric cancer xenograft model was established. A total of 20 mice were divided into two groups (control and experimental groups). The expression of c-Myc and basic fibroblast growth factor (bFGF) was determined by reverse transcription-polymerase chain reaction, Western blotting, and immu-nohistochemical staining methods. Tumor volume was measured and a growth curve was calculated. The tumor diameter in the experimental group was significantly smaller than that in the control group after treat-ment with endostatin for 21 days. The expression levels of c-Myc and bFGF in the experimental group were significantly lower than those of the control group (P < 0.05). There was a positive correlation between the expression of c-Myc and bFGF in the experimental group. Microvessel density was significantly inhibited in the experimental group (P < 0.05). These results demonstrated that recombinant human endostatin could in-hibit tumor metastasis by inhibition of the expression of c-Myc and bFGF in gastric cancer tissue as well as by inhibition of angiogenesis.

Association of DNMT1 and DNMT3B polymorphisms with breast cancer risk in Han Chinese women from South China.

Patterns of DNA methylation are established and maintained by a family of DNA methyltransferases (DNMTs). Aberrant promoter DNA methylation of tumor suppressor genes is found in breast cancer. Association studies between DNMT gene polymorphisms and breast cancer in various populations have reported inconsistent results. This study assessed the associations of single nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A, DNMT3B, DNMT3L, and DNMT2 with breast cancer among Han Chinese women from South China. Sixteen SNPs (rs2114724, rs2228611, rs2228612, rs8101866, and rs16999593 in DNMT1; rs13420827, rs11887120, rs13428812, rs1550117, rs11695471, and rs6733301 in DNMT3A; rs2424908, rs2424913, and rs6087990 in DNMT3B; rs113593938 in DNMT3L, and rs11254413 in DNMT2) in 408 women with breast cancer and 469 controls were genotyped using a MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Two SNPs, rs16999593 in DNMT1 and rs2424908 in DNMT3B, were significantly associated with breast cancer risk. The heterozygous genotype CT of rs16999593 was associated with increased breast cancer risk [odds ratio (OR) = 1.60; 95% confidence interval (95%CI) = 1.20-2.14; P = 0.0052], whereas rs2424908 was associated with decreased risk (OR = 0.62; 95%CI = 0.46-0.84; P = 0.0061). Other DNMT polymorphisms showed no significant associations with breast cancer risk in the study population. Haplotype CGTC of rs2114724, rs2228611, rs8101866, and rs16999593 in DNMT1 differed significantly as a risk factor between the case and control groups (OR = 1.51; 95%CI = 1.18-1.93; P = 0.0012). The heterozygous genotypes of rs16999593 in DNMT1 and rs2424908 in DNMT3B were strongly associated with breast cancer risk.

Expression profiling based on coexpressed modules in obese prepubertal children.

The aim of this study was to identify related genes and the underlying molecular mechanisms in obese patients who show a series of clinical and metabolic abnormalities known as metabolic syndrome. We identified expression profiles through a coexpression network. In addition, a similarity matrix and expression modules were constructed based on domain and pathway enrichment analysis. The genes in module 1 were mainly involved in the metabolism of xenobiotics by cytochrome P450, aldosterone-regulated sodium reabsorption, and focal adhesion owing to the presence of aldo/ketoreductase, basic helix-loop-helix, von Willebrand factor, Frizzled-related domain, and other domains. The genes in module 3 may be involved in cell cycle (hsa04110) and DNA replication (hsa03030) pathways through mini-chromosome maintenance, serine/threonine protein kinase, the protein kinase domain, and other domains. We analyzed the published molecular mechanisms of obesity and found many genes and pathways that have not been given enough attention and require further confirmation.