Additional prognostic value of polymorphisms within the 3′-untranslated region of programmed cell death pathway genes in early-stage breast cancer

IntroductionThe programmed cell death (PCD) pathway plays an important role in restricting cancer cell survival and proliferation. However, limited studies have investigated the association between genetic variants in the 3′-untranslated region of the PCD pathway genes and breast cancer outcomes.MethodsIn this study, we genotyped 28 potentially functional single nucleotide polymorphisms (SNPs) in 23 PCD pathway genes in 1,177 patients with early-stage breast cancer (EBC) from a Han Chinese population. The median follow-up period was 174 months.ResultsAmong all the candidate SNPs, four independent SNPs (rs4900321 and rs7150025 in ATG2B, rs6753785 in BCL2L11, and rs2213181 in c-Kit) were associated with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS) and overall survival (OS), respectively. Further combined genotypes of these four SNPs revealed that the survival decreased as the number of unfavorable genotypes increased (Ptrend = 1.0 × 10−6, 8.5 × 10−8, 3.6 × 10−4, and 1.3 × 10−4 for iDFS, DDFS, BCSS, and OS, respectively). Receiver operating characteristic curve analysis demonstrated that incorporating unfavorable genotypes and clinicopathological variables improved the ability to predict EBC survival (P = 0.006, 0.004, 0.029, and 0.019 for iDFS, DDFS, BCSS, and OS, respectively). Additionally, rs6753785 and rs2213181 were associated with BCL2L11 and c-Kit mRNA expression, respectively.ConclusionsOur results suggest that these four SNPs may act as novel biomarkers for EBC survival, possibly by modulating the expression of the corresponding genes

Associations of two common genetic variants with breast cancer risk in a chinese population: a stratified interaction analysis.

Recent genome-wide association studies (GWAS) have identified a series of new genetic susceptibility loci for breast cancer (BC). However, the correlations between these variants and breast cancer are still not clear. In order to explore the role of breast cancer susceptibility variants in a Southeast Chinese population, we genotyped two common SNPs at chromosome 6q25 (rs2046210) and in TOX3 (rs4784227) in a case-control study with a total of 702 breast cancer cases and 794 healthy-controls. In addition, we also evaluated the multiple interactions among genetic variants, risk factors, and tumor subtypes. Associations of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (95% CI). The results indicated that both polymorphisms were significantly associated with the risk of breast cancer, with per allele OR = 1.35, (95%CI = 1.17-1.57) for rs2046210 and per allele OR = 1.24 (95%CI = 1.06-1.45) for rs4784227. Furthermore, in subgroup stratified analyses, we observed that the T allele of rs4784227 was significantly associated with elevated OR among postmenopausal populations (OR = 1.44, 95%CI 1.11-1.87) but not in premenopausal populations, with the heterogeneity P value of P = 0.064. These findings suggest that the genetic variants at chromosome 6q25 and in the TOX3 gene may play important roles in breast cancer development in a Chinese population and the underlying biological mechanisms need to be further elucidated

Funnel plot and Egger’s test of effect sizes for the included studies.

<p>Funnel plot and Egger’s test of effect sizes for the included studies.</p

Description of Included Trials.

<p>Note: CMF = cyclophosphamide, methotrexate, and 5-fluorouracil regimen; FAC = 5-fluorouracil, doxorubicin, and cyclophosphamide regimen; FSH =  follicle-stimulating hormone; GnRH = gonadotropin-relea sing hormone; NA =  information not available; POF = premature ovarian failure; ^aThis study has four arms: arm A received only chemotherapy ± GnRH analogue; arm B received chemotherapy+ tamoxifen ± GnRH analogue.</p

The Assessment Of Study Quality.

<p>The Assessment Of Study Quality.</p

Forest plot of effect sizes for the incidence of women with spontaneous menstruation.

<p>Forest plot of effect sizes for the incidence of women with spontaneous menstruation.</p

Transcriptional Expressions of CXCL9/10/12/13 as Prognosis Factors in Breast Cancer

CXCLs play critical roles in antitumor immunity by activating tumor-specific immune responses and stimulating tumor proliferation, thus affecting patient outcomes. However, the expression and prognostic values of CXCLs in breast cancer have not been well clarified. The aim of this study was to investigate the impact of CXCLs transcriptional expression on breast cancer patients. Oncomine database, GEPIA (Gene Expression Profiling Interactive Analysis), UALCAN, Kaplan–Meier Plotter, TIMER (Tumor Immune Estimation Resource), and DAVID were used in our study. The transcriptional levels of CXCL9/10/11/13 in breast cancer tissues were significantly elevated while the transcriptional levels of CXCL1/2/3/12 were decreased based on intersections of Oncomine database and GEPIA. Among them, breast cancer patients with high transcriptional levels of CXCL2/9/10/12/13 and low transcriptional level of CXCL3 were associated with a better prognosis. We also found that most of CXCLs expressions are significantly correlated with known prognostic factors, such as patient’s age, major subclasses, individual cancer stages, and nodal metastasis status. In addition, the expression of CXCL9/10/12/13 was also indicated to be correlated with the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). The functions of differentially expressed CXCLs are primarily related to the immune response and cytokine-cytokine receptor interactions. Our results may provide novel evidence of new prognostic or predictive biomarkers for breast cancer patients

Identifying Two Common Types of Breast Benign Diseases Based on Multiphoton Microscopy

Multiphoton microscopy has attracted increasing attention and investigations in the field of breast cancer, based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG). However, the incidence of breast benign diseases is about 5 to 10 times higher than breast cancer; up to 30% of women suffer from breast benign diseases and require treatment at some time in their lives. Thus, in this study, MPM was applied to image fibroadenoma and fibrocystic lesion, which are two of the most common breast benign diseases. The results show that MPM has the capability to identify the microstructure of lobule and stroma in normal breast tissue, the interaction of compressed ducts with surrounding collagen fiber in fibroadenoma, and the architecture of cysts filled with cystic fluid in fibrocystic disease. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time diagnosis of breast benign diseases in vivo, as well as breast cancer

The combined effects of rs2046210 and rs4784227.

a<p>Adjusted by age, BMI, age at menarche, age at first live birth, menopausal status and family history breast cancer where appropriate.</p>b<p>The risk allele included rs2046210-A and rs4784227-T.</p><p>The combined effects of rs2046210 and rs4784227.</p