A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.

Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells.

The efficacy of osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, has been evaluated in glioblastoma (GBM) through preclinical and clinical trials. However, the underlying mechanism of osimertinib-induced GBM cell death and the underlying resistance mechanism to osimertinib remains unclear. Here, we demonstrate that Osimertinib induces paraptosis in GBM cells, as evidenced by the formation of cytoplasmic vacuoles, accumulation of ubiquitinated proteins, and upregulation of endoplasmic reticulum (ER) stress markers like CHOP. Additionally, neither apoptosis nor autophagy was involved in the osimertinib-induced cell death. RNAseq analysis revealed ER stress was the most significantly downregulated pathway upon exposure to osimertinib. Consistently, pharmacologically targeting the PERK-eIF2α axis impaired osimertinib-induced paraptosis. Notably, we show that the expression of thyroid receptor-interacting protein 13 (TRIP13), an AAA+ATPase, alleviated osimertinib-triggered paraptosis, thus conferring resistance. Intriguingly, MK-2206, an AKT inhibitor, downregulated TRIP13 levels and synergized with Osimertinib to suppress TRIP13-induced high GBM cell growth in vitro and in vivo. Together, our findings reveal a novel mechanism of action associated with the anti-GBM effects of osimertinib involving ER stress-regulated paraptosis. Furthermore, we identify a TRIP13-driven resistance mechanism against Osimertinib in GBM and offer a combination strategy using MK-2206 to overcome such resistance.

Risk factors for in-hospital death in 2,179 patients with acute aortic dissection.

Background: This study aims to investigate the risk factors for in-hospital death in patients with acute aortic dissection (AAD) and to provide a straightforward prediction model to assist clinicians in determining the outcome of AAD patients. Methods: Retrospective analysis was carried out on 2,179 patients admitted for AAD from March 5, 1999 to April 20, 2018 in Wuhan Union Hospital, China. The risk factors were investigated with univariate and multivariable logistic regression analysis. Results: The patients were divided into two groups: Group A, 953patients (43.7%) with type A AAD; Group B, 1,226 patients (56.3%) with type B AAD. The overall in-hospital mortality rate was 20.3% (194/953) and 4% (50/1,226) in Group A and B respectively. The multivariable analysis included the variables that were statistically significant predictors of in-hospital death (P < 0.05). In Group A, hypotension (OR = 2.01, P = 0.001) and liver dysfunction (OR = 12.95, P < 0.001) were independent risk factors. Tachycardia (OR = 6.08, P < 0.001) and liver dysfunction (OR = 6.36, P < 0.05) were independent risk factors for Group B mortality. The risk factors of Group A were assigned a score equal to their coefficients, and the score of -0.5 was the best point of the risk prediction model. Based on this analysis, we derived a predictive model to help clinicians determine the prognosis of type A AAD patients. Conclusions: This study investigate the independent factors associated with in-hospital death in patients with type A or B aortic dissection, respectively. In addition, we develop the prediction of the prognosis for type A patients and assist clinicians in choosing treatment strategies.

The clinical efficacy of collagen dressing on chronic wounds: A meta-analysis of 11 randomized controlled trials.

Objective: This study aims to evaluate the clinical efficacy of collagen dressing for patients with chronic wounds. Materials and methods: Relevant randomized controlled trials were searched from the databases such as PubMed, EMBASE, and the Cochrane library as of January 2022. For dichotomous outcomes and continuous outcomes, risk ratio and mean difference were calculated, respectively. Subgroup analysis was performed according to the type of chronic ulcer and follow-up. In addition, trial sequential analysis (TSA) was performed to further verify the results. Jadad score was used to assess the quality of trials. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was utilized to assess the level of evidence for outcomes. Results: In 11 studies, a total of 961 patients of whom 485 were in the collagen group. Compared with standard of care (SOC) alone, the group that added an extra collagen dressing achieved a higher wound healing rate (Risk Ratio = 1.53; 95% CI, 1.33-1.77). The collagen group also showed a higher healing velocity than the SOC group (Mean Difference, 2.69; 95% CI, 0.87-4.51). In addition, the adverse events related to dressing between the two groups were similar (Risk Ratio = 0.67; 95% CI, 0.44-1.01). Conclusion: Collagen dressing increases the wound healing rate and may be an effective and safe treatment for chronic wound management. However, more extensive research shall be conducted to substantiate these results. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=245728, identifier: CRD42021245728.

SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway.

Ferroptosis is a new kind of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Cancer cells differ in their sensitivity to ferroptosis. Here we showed that the Suppressor of fused homolog (SUFU), a critical component in Hedgehog signaling, regulates ferroptosis sensitivity of breast cancer cells. Ectopic SUFU expression suppressed, whereas depletion of SUFU enhanced the sensitivity of breast cancer cells to RSL3-triggered ferroptosis through deregulation of ACSL4. Moreover, SUFU depletion promoted the activation of Yes-associated protein (YAP), thereby increasing the expression of ACSL4. Mechanistically, SUFU is associated with LATS1. Deletion of a region comprising residues 174-385 in SUFU disrupted SUFU binding to LATS1, thus abrogating SUFU-mediated downregulation of the YAP-ACSL4 axis and sensitivity to ferroptosis. Noteworthy, we showed that vincristine downregulated SUFU, thus increasing breast cancer cell sensitivity to RSL3 in vitro and in vivo. Together, our findings uncover SUFU as a novel regulator in ferroptosis sensitivity.

The Application of Platelet-Rich Plasma for Patients Following Total Joint Replacement: A Meta-Analysis of Randomized Controlled Trials and Systematic Review.

Background: The clinical efficacy of platelet-rich plasma (PRP) in the treatment of total joint replacement (TJR) remains inconclusive. In this paper, systematic review and meta-analysis was adopted to assess the efficacy of using PRP for the treatment of TJR. Methods: A comprehensive search of Medline, Embase, and Cochrane library databases for randomized controlled trial (RCT) articles recording data of PRP for TJR was conducted from inception to February 2022. Outcomes concerned were pain, range of motion (ROM), WOMAC score, length of hospital stay (LOS), hemoglobin (Hb) drop, total blood loss, wound healing rate, and wound infection. The methodological quality of the included RCTs was evaluated by using the Cochrane Risk of Bias Tool 2.0 (RoB 2.0). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was utilized to assess the level of evidence for the outcomes. Subgroup analysis was conducted according to the type of TJR. Results: Ten RCTs were included in the meta-analysis. In the TKA subgroup, the available data demonstrated that there were significant differences in the outcomes of pain and Hb drop, while it was the opposite of ROM, WOMAC score, LOS, total blood loss, wound healing rate, and wound infection. In the THA subgroup, no significant differences could be seen between two groups in the outcomes of LOS and wound infection. However, the PRP group gained a higher wound healing rate in the THA subgroup. Conclusion: The application of PRP did not reduce blood loss but improved the wound healing rate. However, more prospective and multicenter studies are warranted to confirm these results.

Analysis of the key prognostic genes and potential traditional Chinese medicine therapeutic targets in glioblastoma based on bioinformatics and network pharmacology methods.

Background: To analyze the key prognostic genes and potential traditional Chinese medicine targets in glioblastoma (GBM) by bioinformatics and network pharmacology. Methods: GBM datasets were obtained from the Gene Expression Omnibus (GEO) database to clarify the differentially-expressed genes (DEGs) in the carcinoma and paracancerous tissues. The molecular functions (MF) and signaling pathways of enriched DEGs were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The STRING database and Cytoscape software were used to construct the protein-protein interaction (PPI) network and screen hub genes to focus on genes with greater clinical significance. The transcription expression and prognosis of hub genes were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database. The important compounds and target molecules were obtained via the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. We identified the active ingredients by setting the property values of pharmacokinetic attribute values. We constructed the network of "Chinese medicine ingredients-DEGs target" and screened out the target genes and active ingredients with high correlation scores. Finally, molecular docking verification was carried out using AutoDock Tools and PyMOL. Results: We obtained 271 DEGs, including 212 up-regulated genes and 59 down-regulated genes and screened ten hub genes. GO and KEGG analyses suggested that the hub genes were mainly involved in the following biological processes: the cell cycle, cell division, and cell adhesion, as well as extracellular matrix adhesion-related pathways, the p53 signaling pathways, and cadherin binding involved in cell-cell adhesion. We established the interaction network between the components and DEGs to screen out the traditional Chinese medicine active component (luteolin) and target genes (BIRC5 and CCNB1) for the treatment of GBM. The molecular docking results showed that the bindings of protein receptors, BIRC5 and CCNB1, with the compound ligand, luteolin, were stable and formed by hydrogen bonding interaction. Conclusions: In this study, we determined that luteolin potentially inhibits glioblastoma proliferation and migration through key target genes, BIRC5 and CCNB1, via bioinformatics and network pharmacology analysis, and affects the prognosis of GBM patients, providing new ideas for clinical targeted therapy and new drug development.

3D Printing of Monolithic Proteinaceous Cantilevers Using Regenerated Silk Fibroin.

Silk fibroin, regenerated from Bombyx mori, has shown considerable promise as a printable, aqueous-based ink using a bioinspired salt-bath system in our previous work. Here, we further developed and characterized silk fibroin inks that exhibit concentration-dependent fluorescence spectra at the molecular level. These insights supported extrusion-based 3D printing using concentrated silk fibroin solutions as printing inks. 3D monolithic proteinaceous structures with high aspect ratios were successfully printed using these approaches, including cantilevers only supported at one end. This work provides further insight and broadens the utility of 3D printing with silk fibroin inks for the microfabrication of proteinaceous structures.

An efficient method of inducing differentiation of mouse embryonic stem cells into primitive endodermal cells.

Primitive Endoderm (PrE) is an extraembryonic structure derived from inner cell mass (ICM) in the blastocysts. Its interaction with the epiblast is critical to sustain embryonic growth and embryonic pattern. In this study, we reported a simple and efficient method to induce the differentiation of mouse Embryonic Stem Cells (mESCs) into PrE cells. In the process of ESC monolayer adherent culture, 1 µM atRA and 10 µM CHIR inducers were used to activate RA and Wnt signaling pathways respectively. After 9 days of differentiation, the proportion of PrE cells was up to 85%. Further studies indicated that Wnt signaling pathway acted as a switch that RA induces mESCs differentiation between SMC and PrE cell. In the presence of only RA signaling, mESCs adopted the fate of smooth muscle cells (SMCs); Simultaneous activation of the Wnt signaling pathway changed the differentiation fate of mESCs into PrE cells. This efficient induction method can provide new cellular resources and models for relevant studies of PrE.

Fiber-Based Biopolymer Processing as a Route toward Sustainability.

Some of the most abundant biomass on earth is sequestered in fibrous biopolymers like cellulose, chitin, and silk. These types of natural materials offer unique and striking mechanical and functional features that have driven strong interest in their utility for a range of applications, while also matching environmental sustainability needs. However, these material systems are challenging to process in cost-competitive ways to compete with synthetic plastics due to the limited options for thermal processing. This results in the dominance of solution-based processing for fibrous biopolymers, which presents challenges for scaling, cost, and consistency in outcomes. However, new opportunities to utilize thermal processing with these types of biopolymers, as well as fibrillation approaches, can drive renewed opportunities to bridge this gap between synthetic plastic processing and fibrous biopolymers, while also holding sustainability goals as critical to long-term successful outcomes.

Interfering with CALCRL expression inhibits glioma proliferation, promotes apoptosis, and predicts prognosis in low-grade gliomas.

Background: CALCRL is involved in a variety of key biological processes, including cell proliferation, apoptosis, angiogenesis, and inflammation. However, the role of CALCRL in glioma remains unknown. The purpose of this study was to investigate the effect of differential CALCRL expression on the malignant progression of glioma and its value in glioma prognosis. Methods: Sequencing data from glioma and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and the downloaded data were statistically analyzed using bioinformatics tools and the corresponding R package. The expression of CALCRL in normal brain tissue and different grades of glioma tissue was detected by pathological and immunohistochemical staining of clinical glioma specimens. The expression of CALCRL in different glioma cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the U87 cell line with high expression was selected to construct the CALCRL knockdown model by transfection with short hairpin (shRNA). The cell proliferation ability was detected by Celigo assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the ability of cell clone formation was detected by clone formation assay, and the level of apoptosis was detected by flow cytometry. Results: The expression of CALCRL in glioma was significantly upregulated compared with that of normal tissue, especially in low-grade glioma (LGG) compared to glioblastoma, and the differential expression of CALCRL correlated significantly with the prognosis of LGG. Clinical pathology and immunohistochemistry showed that the expression of CALCRL was related to the pathological grade of glioma, and the highest expression was found in World Health Organization (WHO) grade Ⅲ glioma. The results of qRT-PCR showed that CALCRL expression was highest in the U87 cell line. After knockdown of CALCRL expression, the proliferation and clonogenic ability of U87 cells were significantly decreased, and the apoptosis rate was significantly increased. Conclusions: CALCRL is highly expressed in LGG. Interfering with CALCRL expression inhibits glioma cell proliferation and promotes apoptosis, and thus has potential as a biomarker and therapeutic target for the prognosis of those with LGGs.

Bio-Based Flame-Retardant Coatings Based on the Synergistic Combination of Tannic Acid and Phytic Acid for Nylon-Cotton Blends.

Natural and synthetic polymeric fibers are used extensively in making fabrics for a variety of civilian and military applications. Due to the durability and comfort, nyco, a 50-50% blend of nylon 66 and cotton, is used as the material of choice in many applications including military uniforms. This fabric is flammable due to the presence of cotton and nylon but has good mechanical properties and is comfortable to wear. Here, we report a novel surface functionalization method that utilizes a synergistic combination of bio-based materials, tannic acid (TA) and phytic acid (PA), to impart flame-retardant (FR) properties to the nyco fabric. TA and PA were sequentially attached to nylon and cotton fibers through hydrogen bonding interactions and phosphorylation, respectively. The surface functionalization of the treated fabrics was confirmed using Fourier-transform infrared spectroscopy. Thermogravimetric analysis, microscale combustion calorimetry, cone calorimetry, and vertical flame testing were employed to study the effect of the functionalization on the thermal stability and flammability of the nyco fabric. Though reasonable durable functionalization is observed from elemental analysis, it is not enough to impart wash-durable FR treatment. These results indicate that flame retardancy is enabled through the enhanced char formation provided by the combination of TA and PA. The TA-PA system applied to nyco shows great promise as a bio-based FR system. This study for the first time also provides evidence for the selectivity of TA in imparting FR characteristics for nylon and PA in imparting FR properties for cotton. The combination of TA and PA provides promising FR characteristics to nyco.

A Novel Method for Source Tracking of Chemical Gas Leakage: Outlier Mutation Optimization Algorithm.

Chemical industrial parks, which act as critical infrastructures in many cities, need to be responsive to chemical gas leakage accidents. Once a chemical gas leakage accident occurs, risks of poisoning, fire, and explosion will follow. In order to meet the primary emergency response demands in chemical gas leakage accidents, source tracking technology of chemical gas leakage has been proposed and evolved. This paper proposes a novel method, Outlier Mutation Optimization (OMO) algorithm, aimed to quickly and accurately track the source of chemical gas leakage. The OMO algorithm introduces a random walk exploration mode and, based on Swarm Intelligence (SI), increases the probability of individual mutation. Compared with other optimization algorithms, the OMO algorithm has the advantages of a wider exploration range and more convergence modes. In the algorithm test session, a series of chemical gas leakage accident application examples with random parameters are first assumed based on the Gaussian plume model; next, the qualitative experiments and analysis of the OMO algorithm are conducted, based on the application example. The test results show that the OMO algorithm with default parameters has superior comprehensive performance, including the extremely high average calculation accuracy: the optimal value, which represents the error between the final objective function value obtained by the optimization algorithm and the ideal value, reaches 2.464e-15 when the number of sensors is 16; 2.356e-13 when the number of sensors is 9; and 5.694e-23 when the number of sensors is 4. There is a satisfactory calculation time: 12.743 s/50 times when the number of sensors is 16; 10.304 s/50 times when the number of sensors is 9; and 8.644 s/50 times when the number of sensors is 4. The analysis of the OMO algorithm's characteristic parameters proves the flexibility and robustness of this method. In addition, compared with other algorithms, the OMO algorithm can obtain an excellent leakage source tracing result in the application examples of 16, 9 and 4 sensors, and the accuracy exceeds the direct search algorithm, evolutionary algorithm, and other swarm intelligence algorithms.

Association Between TNF-α-308, +489, -238 Polymorphism, and COPD Susceptibility: An Updated Meta-Analysis and Trial Sequential Analysis.

The tumor necrosis factor alpha (TNF-α) polymorphism may play an important role in chronic obstructive pulmonary disease (COPD) susceptibility. However, the results are still inconclusive. Eligible studies were searched in Cochrane Library database, EMBASE, Pudmed, Web of science, China National Knowledge Infrastructure, and Wanfang database. Finally, a total of 27 case-control studies with 3473 COPD cases and 4935 controls were included in the present analysis. We also performed trial sequential analysis (TSA) to confirm our results. Overall, association between TNF-α-308G/A polymorphism and COPD susceptibility was identified in allelic model (A vs. G, OR = 1.21, 95%CI: 1.01-1.45, p = 0.04) when smoking status was not adjusted. In ethnicity subgroup analysis, we found that the TNF-α -308G/A polymorphism was associated to COPD among Asians (GA vs. GG, OR = 1.35, 95%CI: 1.04-1.77, p = 0.02) when smoking status was not adjusted. However, no significant association was found in Asian smokers or Caucasian smokers. In conclusion, our study suggest that TNF-α-308 GA genotype is related to COPD in the Asian population. In addition, the TNF-α+489G/A, - 238G/A variants do not increase the risk of COPD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021273980.

Joint Genetic Analyses of Mitochondrial and Y-Chromosome Molecular Markers for a Population from Northwest China.

The genetic markers on mitochondria DNA (mtDNA) and Y-chromosome can be applied as a powerful tool in population genetics. We present a study to reveal the genetic background of Kyrgyz group, a Chinese ethnic group living in northwest China, and genetic polymorphisms of 60 loci on maternal inherited mtDNA and 24 loci on paternal inherited Y-chromosome short tandem repeats (Y-STRs) were investigated. The relationship between the two systems was tested, and the result indicated that they were statistically independent from each other. The genetic distances between Kyrgyz group and 11 reference populations for mtDNA, and 13 reference populations for Y-STRs were also calculated, respectively. The present results demonstrated that the Kyrgyz group was genetically closer to East Asian populations than European populations based on the mtDNA loci but the other way around for the Y-STRs. The genetic analyses could largely strengthen the understanding for the genetic background of the Kyrgyz group.

Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk.

BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology. METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2. RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ). CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

A small NGS-SNP panel of ancestry inference designed to distinguish African, European, East, and South Asian populations.

In this study, a small set of ancestry informative SNPs was selected to differentiate African, European, East and South Asian samples, which was detected by the next-generation sequencing technology. A total of 127 Chinese Shaanxi Han individuals were collected as test samples. No statistically significant linkage disequilibrium of any pair of loci or departure from Hardy-Weinberg equilibrium of each locus was observed in the test population. To evaluate the performance of ancestry assignment using this panel, admixture analysis, principal component analysis, and likelihood ratio calculations were conducted based on the 1000 genome data and test samples. All populations were clustered into four groups, African, European, South and East Asian populations, which were consistent with their geographical origins. The pairwise fixation index (FST ) between populations from different continental groups ranged from 0.140 to 0.621 with average 0.415, and the pairwise FST between populations from the same continent ranged from 0.000 to 0.056 with average 0.012. The likelihood ratio results of 125 test individuals indicated that their ancestry components were highly possible from East Asia. In conclusion, this small set of ancestry informative SNPs can be used as a reliable tool to identify and quantify ancestry components of unknown samples.

A reinforced thermal barrier coat of a Na-tannic acid complex from the view of thermal kinetics.

The poor burning resistance of cotton necessitates the control of its pyrolytic reactions, but many approaches have relied on the use of synthetically engineered chemicals. Herein, we show how a natural polyphenol from plants-tannic acid-acts with sodium ions to create a robust thermal barrier coat on cotton, with a focus on thermal kinetics. The kinetic information, combined with thermal and spectral analyses, revealed that the outer layer of galloyl units in tannic acid decomposes via a two-step reaction, producing a multicellular char of crosslinked aromatic rings, followed by the blowing of carbonaceous cells into a further expanded structure. This intumescent function of tannic acid was found to be enhanced upon its complexation with sodium ions, which greatly increased the activation energy for the first step of the reaction of tannic acid, to promote the formation of a stable char. The resulting blown char coated the cotton fiber below the thermal decomposition temperature of cellulose and was sustained throughout the decomposition. The enhanced thermal barrier performance of the Na-tannic acid complex was demonstrated by the reduced heat release capacity of cotton, the value of which was only about one-third that of tannic acid itself, and the inhibition of flame generation on cotton.

Associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white women diagnosed with breast cancer: the Breast Cancer Health Disparities Study.

PURPOSE: ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is involved in the differentiation and protection of normal hematopoietic stem cells and functions in alcohol sensitivity and dependence. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the Breast Cancer Health Disparities Study. METHODS: Nine SNPs in ALDH1A1 were evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC. Adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were stratified by Native American (NA) ancestry and alcohol consumption. RESULTS: A total of 443 deaths occurred over a median follow-up time of 11 years. After adjusting all results for multiple comparisons, rs7027604 was significantly associated with all-cause mortality (HRAA = 1.40; 95% CI 1.13-1.73, P adj = 0.018). The rs1424482 CC genotype (HRCC = 1.69; 95% CI 1.20-2.37, P adj = 0.027) and the rs7027604 AA genotype (HRAA = 1.65; 95% CI 1.21-2.26, P adj = 0.018) were positively associated with non-BC mortality. Among long-term light drinkers, rs1888202 was associated with decreased all-cause mortality (HRCG/GG = 0.36; 95% CI 0.20-0.64), while associations were not significant among non-drinkers or moderate/heavy drinkers (P interation = 0.218). The increased risk of all-cause mortality associated with rs63319 was limited to women with low NA ancestry (HRAA = 1.53; 95% CI 1.19-1.97). CONCLUSIONS: Multiple SNPs in ALDH1A1 were associated with increased risk of mortality after BC. Future BC studies examining the relationship between ALDH1A1 and mortality should consider the modifying effects of alcohol consumption and NA ancestry.