OBJECTIVETo explore the application of counter-matching design in epidemiological research.

METHODSThrough elaboration of the study about gene-environment interactions in the etiology of breast cancer, methodology regarding counter-matching design and statistic methods was introduced.

RESULTSThis design improved the potential for detecting gene-environment interactions for diseases when both gene mutations and the environmental exposures of interest were rare in the general population.

CONCLUSIONCounter-matching appearsed to be more appropriate than most traditional epidemiologic methods for the study of interactions involving rare factors.

Breast Neoplasms ; epidemiology ; etiology ; genetics ; radiotherapy ; Epidemiologic Methods ; Humans ; Male

OBJECTIVETo evaluate the frequency and nature of E-cadherin gene (CDH1) germline mutations in familial gastric cancer kindreds of china.

METHODSFive familial gastric cancer kindreds of Chinese origin were screened for germline CDH1 mutations, all of them meeting the clinical criteria for hereditary diffuse gastric cancer (HDGC), by PCR-DHPLC and direct sequencing.

RESULTSA new truncating mutation in exon 10 in B family was identified, producing a stop codon at position 503 (Q503X), resulting in a truncated protein. The proband of this family had metachronous development of lobular breast and diffuse type gastric carcinoma. No protein expression was detected in the lobular breast carcinoma, indicating complete inactivation of the gene.

CONCLUSIONSA Chinese gastric cancer family with CDH1 germline truncating mutation is described for the first time, and our findings suggest that lobular breast carcinoma might be part of the tumor spectrum of HDGC.

Adult ; Breast Neoplasms ; genetics ; Cadherins ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasms, Multiple Primary ; genetics ; Neoplastic Syndromes, Hereditary ; genetics ; Pedigree ; Polymerase Chain Reaction ; Stomach Neoplasms ; genetics

OBJECTIVETo investigate the expression of the human mammoglobin (hMAM) mRNA in bone marrow and its clinical significance in the breast cancer patient.

METHODSExpression of hMAM mRNA was detected using nested reverse transcription polymerase chain reaction (RT-PCR) in the bone marrow aspiration sample from 75 breast cancer patients, 15 patients with benign breast lesions and 8 healthy volunteers as control. The possible correlation of hMAM mRNA expression with clinico-pathological parameters and related molecular markers such as Ki67, p53 and VEGF were analyzed.

RESULTSThe sensitivity of RT-PCR in this series reached 10(-6). The hMAM mRNA was found to be positively expressed by RT-PCR in 21 of 75 breast cancer patients with a positive rate of 28.0%. However, hMAM mRNA expression was not detected in the bone marrow aspiration samples from patients with benign breast lesions and healthy volunteers. The hMAM mRNA expression was positively correlated with axillary nodal involvement and progesterone receptor (PR) status (P < 0.05) as well as Ki67 expression in breast cancer tissue (chi2 = 4.936, P = 0.026), but not with age, tumor size, clinical stage, or estrogen receptor (ER) status (P > 0.05).

CONCLUSIONRT-PCR is quite sensitive and has a high specificity in detecting the presence of hMAM mRNA in the bone marrow from breast cancer patients. Thereupon, hMAM mRNA may be useful as a molecular biomarker in detecting disseminated tumor cells (DTC) in the bone marrow of breast cancer patients. Positive hMAM mRNA expression result may have an impact upon therapeutic recommendations and patients' prognostic judgement.

Adult ; Aged ; Biomarkers, Tumor ; genetics ; Bone Marrow ; metabolism ; pathology ; Breast ; metabolism ; pathology ; Breast Neoplasms ; genetics ; pathology ; Breast Neoplasms, Male ; genetics ; pathology ; Carcinoma, Ductal, Breast ; genetics ; pathology ; Female ; Fibroadenoma ; genetics ; pathology ; Humans ; Ki-67 Antigen ; genetics ; Lymphatic Metastasis ; Male ; Mammaglobin A ; Middle Aged ; Neoplasm Proteins ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, Progesterone ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Uteroglobin ; genetics

OBJECTIVE: To explore the genetic basis for a male with breast cancer and a sister who had deceased of the disease. METHODS: Medical and family history of the proband was collected. Next-generation sequencing was carried out to detect potential variant associated with breast cancer, and Sanger sequencing was used to verify the result. RESULTS: The proband was found to harbor a novel heterozygous c.6018dupT variant of the BRCA2 gene which may cause premature termination of mRNA translation, resulting in a truncated protein. Combined with the family history, the variant was deduced to be a germline mutation. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.6018dupT variant of BRCA2 gene was predicted to be pathogenic (PVS1+PM1/2+PP4). CONCLUSION The germline variant of the BRCA2 gene probably underlay the breast cancer in this pedigree.
BRCA2 Protein/genetics* ; Breast Neoplasms, Male/genetics* ; Genes, BRCA2 ; Genomics ; Germ Cells ; Germ-Line Mutation ; Humans ; Male

Breast Neoplasms ; genetics ; metabolism ; Female ; Gene Expression Profiling ; Humans ; Male ; Oligonucleotide Array Sequence Analysis ; methods

OBJECTIVETo investigate the different expressions of ER and ER gene status between primary and relapsed/metastatic lesions and their clinical significance.

METHODSER and ER gene status of primary and relapse/metastatic breast cancer masked in 70 metastatic breast cancer patients were assessed by determination of methylation status by immunohistochemistry (IHC) and methylation specific polymerase chain reaction (MSP), respectively.

RESULTSPositive rate of ER in the primary breast cancers was 64.3%, and in the relapse/metastatic lesions was 41.4% (P < 0.05). There were six patients whose positive ER status was changed to negative, among them the ER gene status was changed from demethylation to hypermethylation in four cases. Another four patients with negative ER status changed to positive, and their ER gene hypermethylation changed to ER demethylation status.

CONCLUSIONSThe discordance of ER expression status in primary and relapse/metastatic lesions of breast cancer might be related to DNA methylation status.

Adult ; Aged ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Breast Neoplasms, Male ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; secondary ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Lung Neoplasms ; genetics ; metabolism ; secondary ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, Estrogen ; genetics ; metabolism

OBJECTIVETo observe the sensitivity of the PC-3 cell lines transfected with the PCI-NEO-SNCG plasmid to Cisplatin (DDP), 5-Fluorouracil (5-FU), Adriamycin (ADM), Vincristine (VCR) and Paclitaxel (TAX), and to explore the influence of the SNCG expression on the effectiveness of anti-tumor drugs.

METHODSThe plasmids PCI-NEO and PCI-NEO-SNCG were transfected into the hormone-independent prostate cancer cell lines PC-3. RT-PCR was adopted to examine the expression of SNCG in the PC-3 cell lines. The MTT method was employed to detect the suppressive effects of different anti-tumor drugs (DDP, ADM, 5-FU, VCR and TAX) on the cell lines transfected with PCI-NEO and PCI-NEO-SNCG. Flow cytometry was used to analyze the cell cycles and apoptosis of the transfected cells treated with TAX.

RESULTSThe 5 anti-tumor drugs suppressed the growth of the cell lines transfected with the plasmids PCI-NEO and PCI-NEO-SNCG in a time-dependant manner. The comparison between the growth-suppressing effects of different anti-tumor drugs on the PC-3 cell lines showed no significant differences between the group transfected with PCI-NEO and that with PCI-NEO-SNCG in DDP, 5-FU, ADM and VCR (P > 0.05), while the rate of suppression of TAX on the latter cell lines was significantly lower than that on the former (P < 0.01). Compared with the PCI-NEO-SNCG plasmid transfected cell lines, after treated with TAX for 48 hours, those transfected with the PCI-NEO plasmid exhibited a significantly larger proportion of cells remaining in the G2-M stage (P < 0.01), a smaller proportion in the G0-G1 and S stages (P < 0.01) and a significantly higher expression of Caspase-3 (P < 0.01).

CONCLUSIONThe significant reduction of the growth-suppressing effect of TAX in the SNCG-transfected PC-3 cell lines suggests that the expression of SNCG may restrain the effect of TAX. These findings have provided evidence and guide to the individual chemotherapy of prostate cancer.

Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Drug Screening Assays, Antitumor ; Humans ; Male ; Neoplasm Proteins ; genetics ; Paclitaxel ; pharmacology ; Prostatic Neoplasms ; Transfection ; gamma-Synuclein ; genetics

OBJECTIVETo study on mutations in D-loop region which is gene control region of mitochondrial genome in patients with familial breast cancer.

METHODSTwenty-three breast cancer patients came from twenty-one families of breast cancer, and eighteen healthy controls participated in the study. PCR amplification of D-loop region in mitochondrial DNA was performed and then the product was sequenced to analyze mutations.

RESULTSOne hundred and twenty-six mutations in D-loop region were found in twenty-three patients with familial breast cancer, and four mutations were new. In all of twenty-three patients, thirty-seven mutations were found in D310 which was hot spot of D-loop region in mitochondrial DNA. In these mutations, T>C in 310, TC insert in 311-312, CA deletion in 522-523 and C>G in 527 were multi-presentation mutations in patients with familial breast cancer. Mutations had no difference in the same family member of breast cancer family except that occurrence in the region of D310. In the same family, mutations in D310 of patients were different from controls.

CONCLUSIONMutations in D310 of familial breast cancer patients may enhance their susceptibility to breast cancer.

Adult ; Base Sequence ; Breast Neoplasms ; genetics ; DNA, Mitochondrial ; chemistry ; genetics ; Female ; Genetic Predisposition to Disease ; Genome, Human ; genetics ; Humans ; Locus Control Region ; genetics ; Male ; Middle Aged ; Mutation ; Pedigree

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

Breast Neoplasms ; genetics ; metabolism ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Colorectal Neoplasms ; genetics ; metabolism ; Endometrial Neoplasms ; genetics ; metabolism ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Head and Neck Neoplasms ; genetics ; metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; genetics ; metabolism ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; metabolism ; Insulin-Like Growth Factor Binding Protein 5 ; genetics ; metabolism ; Insulin-Like Growth Factor Binding Proteins ; genetics ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; Male ; Ovarian Neoplasms ; genetics ; metabolism ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Prostatic Neoplasms ; genetics ; metabolism