The Impact of CASP8 rs10931936 and rs1045485 Polymorphisms as well as the Haplotypes on Breast Cancer Risk: A Case-Control Study.

INTRODUCTION: Single nucleotide polymorphisms account for most genetic predispositions to breast cancer in the general population. Because of the lack of studies concerning the 2 common polymorphisms in caspase 8 (CASP8), namely rs104548 and rs10931936 in Iranian population, we evaluated the association of these 2 polymorphisms and their haplotypes with breast cancer and molecular profile. MATERIALS AND METHOD: Blood samples were collected from 287 breast cancer patients and 490 controls. Genotyping of rs1045485 and rs10931936 was conducted using an amplification refractory mutation system and polymerase chain reaction restriction fragment length polymorphism, respectively. PHASE version 2 (Matthew Stephens) was used to estimate the frequencies of haplotypes. Statistical analysis was performed using SPSS 16.0 (SPSS Inc). RESULTS: Although hormone receptors and the molecular profile did not indicate any significant association with different genotypes (P > .05), patients with CC genotype of rs1045485 were more likely to have HER2-positive breast cancer than those with GG genotype (odds ratio [OR], 2.93; 95% confidence interval [CI], 1.0 4-8.26). In addition, CC genotype of D302H was associated with a decreased risk of breast cancer to 48% (OR, 0.52; 95% CI, 0.30-0.90) whereas no significant association was found between rs10931936 and breast cancer. Haplotype analysis indicated C-C haplotype is associated with the decreased risk of breast cancer (OR, 0.69; 95% CI, 0.52-0.91). CONCLUSION: Our data showed a protective effect for CC genotype of rs1045485 variant and C-C haplotype of rs10931936-rs104548 in CASP8 in association with the decrease risk of breast cancer whereas rs10931936 showed no significant association. CASP8 rs1045485 polymorphism might be a candidate genetic marker to evaluate risk of breast cancer. However, further larger studies can confirm such findings.

Association of caspase 8 promoter variants and haplotypes with the risk of breast cancer and its molecular profile in an Iranian population: A case-control study.

Caspase 8 (CASP8) gene plays a key role in the regulation of apoptotic cell death. Expression variation in this gene has been associated with the risk of breast cancer. The aim of this study was to investigate the association of rs3834129 and rs3769821, as functional variants, and their haplotypes with molecular profile as well as the risk of breast cancer in an Iranian population. A case-control study was conducted on 812 participants including 293 breast cancer patients and 519 healthy controls. Genotyping was performed by polymerase chain reaction-based methods. Statistical analysis was performed using SPSS Ver16. The association between polymorphisms and haplotypes with the risk of breast cancer was estimated by calculating odds ratios (OR) and chi-square (χ2 ) tests. In comparison with ins allele (I) of rs3834129, carriers of del allele (D) showed a lower risk of breast cancer (OR, 0.65; 95% confidence interval [CI], 0.49-0.87; P = 0.004). The multivariate logistic regression model indicated DD genotype as an independent factor for a decreased risk of breast cancer in our population (OR, 0.18; 95% CI, 0.06-0.58; P = 0.004). Also, the C allele of rs3769821 was associated with a 43% increased risk of breast cancer (P = 0.005); however, after adjustment for confounding factors, no association with rs3769821 and breast cancer was observed. In addition, D-T haplotype and diplotype presented protective effects (P < 0.05). Our results indicate that genetic variations in the promoter region of CASP8 gene, especially rs3834129, may serve as a genetic risk factor for breast cancer in an Iranian population.

Improved chondrogenic response of mesenchymal stem cells to a polyethersulfone/polyaniline blended nanofibrous scaffold.

Owing to the fact that the cartilage tissue is not able to repair itself, the treatment of the joint damages is very difficult by current methods. Induction of tissue repair requires suitable cell and extracellular matrix. Providing these two parts can only be done using tissue engineering. In the present study, polyethersulfone (PES) and polyaniline (PANI) blend was electrospined for nanofibrous scaffold fabrication. Mesenchymal stem cells were isolated from human adipose tissue (AT-MSCs), and after characterization cultured on the PES-PANI scaffold and culture plate. Electron microscopic and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays were used for biocompatibility evaluation of the scaffold and the chondrogenic differentiation potential of AT-MSCs were investigated by staining of proteoglycans and gene and protein expression evaluation. Alcian blue staining, real-time reverse-transcriptase polymerase chain reaction and Western blot results showed that chondrogenic differentiation potential of AT-MSCs was significantly increased when grown on PES-PANI nanofibers and was compared to the one grown on a culture plate. According to the results, PES-PANI has a promising potential to be used as a biomedical implant in patients with joints lesion, such as arthritis and osteoarthritis.