Pleckstrin homology like domain family A member 1(PHLDA1) is also known as T-cell death-associated gene 51 (TDAG51).Studies have demonstrated that the abnormal expression of PHLDA1 is closely associated with the formation,development,and metastasis of tumors.We summarized the latest research advances in the structure and biological properties of PHLDA1,as well as the roles of PHLDA1 in multiple malignanttumors such as breast cancer,cancer,liver gastric cancer,liver cancer,melanoma,and osteosarcoma,aiming to comprehensively reveal the significance of PHLDA1 in the clinical diagnosis of tumors.
Humans ; Female ; Transcription Factors/genetics* ; Phosphoproteins ; Blood Proteins ; Breast Neoplasms/genetics*

Adult ; Aged ; Breast Neoplasms ; blood ; pathology ; Carcinoembryonic Antigen ; blood ; genetics ; Carcinoma, Ductal, Breast ; blood ; secondary ; Female ; Fibroadenoma ; blood ; Fibrocystic Breast Disease ; blood ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; RNA, Messenger ; blood ; genetics

OBJECTIVETo evaluate the association between serum level of leptin and leptin receptor gene (LEPR) polymorphism and patients with breast cancer.

METHODSLEPR G1n223Arg polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 94 patients with breast cancer and 128 healthy controls. The level of leptin were analyzed by enzyme linked immunosorbent assay.

RESULTSIn univariate regression analyses, we found serum level of leptin and LEPR Gin223Arg genotype polymorphism were significantly higrer than those of the controls (P < 0.05-0.001, respectively). Through multivariable analyses, we found that increased risk estimates for breast cancer were among those with leptin level (OR = 1.53, 95% CI: 1.13-2.07, P = 0.006), LEPR Gin223Arg genotype (OR = 4.87, 95%CI:1.30-18.22, P = 0.019), WHR (OR = 3.68, 95% CI: 1.34-10.11, P = 0.011).

CONCLUSIONResults from this study suggested that LEPR Gln233Agr polymorphism, the elevated WHR and serum level of leptin might be correlated with increased risk of breast cancer.

Breast Neoplasms ; blood ; genetics ; Enzyme-Linked Immunosorbent Assay ; Female ; Genetic Predisposition to Disease ; Humans ; Leptin ; blood ; Lipids ; blood ; Polymorphism, Genetic ; Receptors, Leptin ; genetics ; Risk

OBJECTIVETo evaluate the clinical value of mutated p53 in the peripheral blood of breast cancer patients.

METHODSPlasma DNA of 126 breast cancer patients and 92 healthy women was examined. DNA extraction from the tumor and tissue samples was performed by a nonorganic method. Plasma DNA was purified on Qiagen columns. PCR-SSCP analysis was performed to examine the point mutations in the conserved exons 5, 6, 7 and 8 of TP53.

RESULTSThe mean concentration of plasma DNA was 21 ng/ml in healthy women and 211 ng/ml in patients with breast cancer (P < 0.01). p53 mutations in the primary tumor were detected in 46 of 126 (36.5%) breast cancer patients. Of these 46 patients, 30 (65.1%) were also found to have p53 mutations in their plasma DNA. p53 mutation in plasma DNA was closely correlated with clinical stage, tumor size, lymph node (LN) metastasis and estrogen receptor status (P < 0.05). Survival of the patients with both primary tumor and plasma p53 mutations was the worst. Thirteen of the 22 (59.0%) patients with recurrence and/or metastasis had detectable p53 mutations in their plasma DNA.

CONCLUSIONp53 mutations in plasma DNA may be a useful prognostic factor and an early marker of recurrence or distant metastasis in breast cancer.

Adult ; Aged ; Breast Neoplasms ; genetics ; mortality ; Carcinoembryonic Antigen ; blood ; DNA ; blood ; Female ; Humans ; Middle Aged ; Mucin-1 ; blood ; Mutation ; Prognosis ; Tumor Suppressor Protein p53 ; genetics

BACKGROUNDBreast cancer is the most common type of cancer among females. Genetic polymorphisms might have a role in carcinogenesis. The aim of this study was to determine whether C to T base substitution within TaqI Vitamin D receptor (VDR) gene (rs731236) in exon 9 was a risk factor among patients with breast cancer.

METHODSPeripheral blood was drawn from 122 Jordanian breast cancer patients and 100 healthy Jordanian volunteers in Al-Basheer Hospital during the summer months (from June to November of 2013, 2014, and 2015). DNA was amplified using polymerase chain reaction (PCR), followed by TaqI restriction enzyme digestion. Quantification of serum 25-hydroxy Vitamin D (25[OH]D) level was determined by competitive immunoassay Elecsys.

RESULTSGenotypic frequencies for TaqI TT, Tt, and tt genotypes were 41%, 46%, and 13% for breast cancer compared to 42%, 50%, and 8% for control, respectively. Vitamin D serum level was significantly lower in the breast cancer patients (8.1 ± 0.3 ng/ml) compared to the control group (21.2 ± 0.6 ng/ml; P= 0.001). This study showed an inverse association between 25(OH)D serum level and breast cancer risk (odds ratio [OR], 22.72, 95% confidence interval [CI], 10.06-51.29).

CONCLUSIONSAn inverse association was found between 25(OH)D serum level and breast cancer risk. Statistical difference was also found between different VDR TaqI genotypes and circulating levels of 25(OH)D among Jordanian females with breast cancer.

Adult ; Aged ; Breast Neoplasms ; genetics ; Female ; Genetic Predisposition to Disease ; etiology ; Genotype ; Humans ; Male ; Middle Aged ; Receptors, Calcitriol ; genetics ; Risk Factors ; Vitamin D ; analogs & derivatives ; blood ; genetics

OBJECTIVETo study the expression of human mammaglobin (hMAM) mRNA in the peripheral blood of breast cancer patients and its implication.

METHODSThe expression of human mammaglobin mRNA was determined by using RT-PCR method in 56 patients with peripheral blood breast cancer, 8 patients with breast hyperplasia and 8 women with normal breast. The expression of hMAM mRNA was compared with biological significance and change of hMAM mRNA in chemotherapy after operation.

RESULTSThe expression of hMAM mRNA was negative in 8 patients with breast hyperplasia, 8 women with normal breast and 56 patients with breast cancer, The positive rate was 30.4% (17/56) (chi(2) = 19.766, P < 0.01). The expression of hMAM mRNA in peripheral blood was not correlated with clinical stage, primary tumor size and patients age (chi(2) = 1.256, P > 0.05). After short-term large dose of chemotherapy, 41.2% (7/17) patients turned positive before operation to negative hMAM mRNA expression and negetive expression before operation positive expression after chemotherapy.

CONCLUSIONSThis study suggests that hMAM is sensitive and specific for breast cancer. Detection of the expression of hMAM mRNA in peripheral blood of breast cancer is of value in the diagnosis and judgement of prognosis of breast cancer.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Breast Neoplasms ; blood ; diagnosis ; Female ; Gene Expression ; Humans ; Leukocytes, Mononuclear ; metabolism ; Mammaglobin A ; Middle Aged ; Neoplasm Proteins ; blood ; genetics ; Prognosis ; RNA, Messenger ; blood ; Uteroglobin ; blood ; genetics

OBJECTIVETo study the APC and E-cadherin gene promoter hypermethylation as tumor marker and to investigate the correlation of free tumor-related DNA in serum and tumor tissue with clinicopathological parameters. Their feasibility in early diagnosis, predicting therapeutic effect and monitoring recurrence was evaluated.

METHODS84 cases with operated breast cancer were recruited from March 2002 to August 2002 at Beijing Cancer Hospital. Aberrant methylation of E-cadherin and APC genes was detected in tumor tissues, adjacent normal tissues and peripheral blood serum by methylation-specific PCR (MSP). 10 cases with benign breast diseases were selected as control group.

RESULTSThe positive rate of promoter hypermethylation of E-cadherin and APC genes in tumor tissues was 52.4% and 45.2%, in the paired serum was 33.3% and 31.0%, respectively. Aberrant methylation of free DNA in serum presented the same alteration in tumor tissues. E-cadherin and APC hypermethylation in serum and tumor samples significantly correlated each other (E-cadherin P < 0.001; APC P = 0.002). The sensitivity of detection of free DNA methylation of E-cadherin and APC genes in serum was 63.6% and 63.2%, respectively. The specificity was 100% and 95.7%, respectively. There was no correlation for the aberrant methylation in cancer tissues and serum with the clinicopathological parameters of patients including age, tumor staging, tumor size, histological type and receptor. None of the aberrant methylation was found in adjacent normal tissues and control group serum.

CONCLUSIONThe same aberrant methylation in cancer tissues and serum, not correlating with tumor staging, can be detected in about one third of breast cancer patients. The aberrant methylation in serum can disappear after operation. The results imply that this approach may be feasible for early diagnosis, evaluation of therapeutic effects and monitoring recurrence of breast cancers.

Adult ; Aged ; Biomarkers, Tumor ; Breast Neoplasms ; blood ; genetics ; Cadherins ; blood ; genetics ; CpG Islands ; DNA Methylation ; DNA, Neoplasm ; blood ; genetics ; Female ; Genes, APC ; Genes, Tumor Suppressor ; Humans ; Middle Aged ; Promoter Regions, Genetic ; Sensitivity and Specificity ; Young Adult

OBJECTIVETo study the effects of a small interfering RNA targeting CXCR-4 (shRNA-CXCR4) on angiogenesis of human breast cancer cells.

METHODSThe expression of CXCR4 mRNA and protein in 3 breast cancer cell lines with CXCR-4 silencing mediated by shRNA-CXCR4 was detected by RT-PCR and Western blotting, respectively. The morphological changes of human umbilical vein endothelial cells (HUVECs) were observed in co-culture with human breast cancer cells after CXCR4 gene silencing.

RESULTSCXCR4 mRNA and protein expressions decreased significantly in MCF-7, MDA-MB-231 and MDA-MB-435s breast cancer cells after the gene silencing (P<0.05). Gene silencing with shRNA-CXCR4 in human breast cancer cells significantly inhibited the ability of HUVECs to form tubular structures in the co-culture (P<0.05).

CONCLUSIONGene silencing by shRNA-CXCR4 can obviously lower the angiogenesis-inducing ability of human breast cancer cells.

Breast Neoplasms ; blood supply ; genetics ; Cell Line, Tumor ; Coculture Techniques ; Endothelial Cells ; cytology ; Female ; Humans ; Neovascularization, Pathologic ; genetics ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, CXCR4 ; genetics ; metabolism ; Umbilical Veins ; cytology

The endothelial nitric oxide synthase (eNOS) gene plays an important role in several biological functions. Polymorphisms of the eNOS gene have been associated with cancer. It has been suggested that the VNTR 4 a/b polymorphism may affect the expression of eNOS and contributes to tumor promotion in the mammary gland. We examined the role of the eNOS4 a/b polymorphism by comparing the genotypes of 281 healthy Mexican women with the genotypes of 429 Mexican women with breast cancer (BC). The observed genotype frequencies for control and BC patients were 0.6% and 0.7% for a/a (polymorphic); 87% and 77% for a/a (wild type); and 12% and 22% for a/b respectively. We found that the odds ratio (OR) was 1.9, with a 95% confidence interval (95%CI) of 1.29-2.95, P = 0.001 for genotypes a/a-a/b, b/c. The association was also evident when comparing the distribution of the a/a-a/b genotypes in patients with high levels of glutamate-oxaloacetate transaminase (SGOT) (OR, 1.93; 95% CI, 1.14-3.28; P = 0.015); undergoing menopause with high levels of SGOT (OR, 2.0; 95% CI, 1.1-3.84); and with high levels of glutamic-pyruvic transaminase (SGPT) (OR, 3.5; 95% CI, 1.56-8.22). The genotypes a/a-a/b are associated with BC susceptibility in the analyzed samples from the Mexican population.
Adult ; Alanine Transaminase/*blood ; Aspartate Aminotransferases/*blood ; Breast Neoplasms/*blood/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Mexico ; Middle Aged ; Nitric Oxide/biosynthesis/metabolism ; Nitric Oxide Synthase Type III/*genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo study the potential effect of gene-environment interaction between CYP1A1 and serum dichlorodiphenyldichloroethane (DDT) levels on the risk of breast cancer in women, in China.

METHODSA case-control study was conducted. From Dec. 2003 to Sep. 2004, 104 women with histologically confirmed breast cancers and 154 noncancerous controls from a community were enrolled in this study. Risk factors information of breast cancer was investigated by a questionnaire. Serum p, p'-dichlorodiphenyldichloroethane (p, p'-DDT) and 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels were tested by GC-ECD. CYP1A1 m2 gene type was tested by allele special-PCR method.

RESULTSSerum DDT levels of case and control were (36.90 +/- 79.41) ng/ml and (50.60 +/- 150.70) ng/ml respectively. Serum 1, 1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p, p'-DDE) levels of case and control were (7.43 +/- 11.10) ng/ml and (8.96 +/- 11.30) ng/ml respectively. No statistically significant differences were found between the two groups with geometric mean t-test (P > 0.05). Compared with women who had homozygous wild-type CYP1A1 m2 genotype, significantly increased risks of breast cancer were found for women with the CYP1A1 m2 homozygous variant genotype [odds ratio (OR) = 2.61, 95% confidence interval (CI): 1.00 - 6.80]. Among premenopausal women, compared with women with homozygous wild-type of CYP1A1 genotype (Ile/Ile) and low serum DDT level (DDT serum level < or = 42.93 ng/ml), women with at least one variant allele of CYP1A1 m2 genotype and high serum DDT level (DDT serum level > or = 42.93 ng/ml) had higher risk of breast cancer (OR = 4.35, 95% CI: 1.140 - 16.950).

CONCLUSIONSCYP1A1 m2 genetic polymorphism was associated with increased risk of female breast cancer while DDT exposure might have increased the risk of breast cancer among premenopausal women with CYP1A1 m2 variant genotype.

Breast Neoplasms ; epidemiology ; etiology ; genetics ; Case-Control Studies ; China ; epidemiology ; Cytochrome P-450 CYP1A1 ; genetics ; Dichlorodiphenyl Dichloroethylene ; blood ; Dichlorodiphenyldichloroethane ; blood ; Environmental Exposure ; adverse effects ; Female ; Genotype ; Homozygote ; Humans ; Insecticides ; blood ; Odds Ratio ; Polymorphism, Genetic ; Premenopause ; Risk Factors