Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank.

Several breast cancer susceptibility genes have been discovered, but more are likely to exist. To identify additional breast cancer susceptibility genes, we used the founder population of Poland and performed whole-exome sequencing on 510 women with familial breast cancer and 308 control subjects. We identified a rare mutation in ATRIP (GenBank: NM_130384.3: c.1152_1155del [p.Gly385Ter]) in two women with breast cancer. At the validation phase, we found this variant in 42/16,085 unselected Polish breast cancer-affected individuals and in 11/9,285 control subjects (OR = 2.14, 95% CI = 1.13-4.28, p = 0.02). By analyzing the sequence data of the UK Biobank study participants (450,000 individuals), we identified ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR = 3.28, 95% CI = 1.76-6.14, p < 0.001). Immunohistochemistry and functional studies showed the ATRIP c.1152_1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress. We showed that tumors of women with breast cancer who have a germline ATRIP mutation have loss of heterozygosity at the site of ATRIP mutation and genomic homologous recombination deficiency. ATRIP is a critical partner of ATR that binds to RPA coating single-stranded DNA at sites of stalled DNA replication forks. Proper activation of ATR-ATRIP elicits a DNA damage checkpoint crucial in regulating cellular responses to DNA replication stress. Based on our observations, we conclude ATRIP is a breast cancer susceptibility gene candidate linking DNA replication stress to breast cancer.

New classifications for quantum bioinformatics: Q-bioinformatics, QCt-bioinformatics, QCg-bioinformatics, and QCr-bioinformatics.

Bioinformatics has revolutionized biology and medicine by using computational methods to analyze and interpret biological data. Quantum mechanics has recently emerged as a promising tool for the analysis of biological systems, leading to the development of quantum bioinformatics. This new field employs the principles of quantum mechanics, quantum algorithms, and quantum computing to solve complex problems in molecular biology, drug design, and protein folding. However, the intersection of bioinformatics, biology, and quantum mechanics presents unique challenges. One significant challenge is the possibility of confusion among scientists between quantum bioinformatics and quantum biology, which have similar goals and concepts. Additionally, the diverse calculations in each field make it difficult to establish boundaries and identify purely quantum effects from other factors that may affect biological processes. This review provides an overview of the concepts of quantum biology and quantum mechanics and their intersection in quantum bioinformatics. We examine the challenges and unique features of this field and propose a classification of quantum bioinformatics to promote interdisciplinary collaboration and accelerate progress. By unlocking the full potential of quantum bioinformatics, this review aims to contribute to our understanding of quantum mechanics in biological systems.

Recontact to return new or updated PALB2 genetic results in the clinical laboratory setting.

OBJECTIVE: The purpose of this study was to recontact individuals with clinically actionable test results identified through a retrospective research study and to provide a framework for laboratories to recontact patients. METHODS: Genetic testing was conducted on 2977 individuals originally referred for BRCA1 and BRCA2 hereditary breast and ovarian cancer testing that had a negative genetic test result. A gene panel was used to identify pathogenic variants in known or newly discovered genes that could explain the underlying cause of disease; however, analysis was restricted to PALB2 for the purposes of this study. A patient recontact decision tree was developed to assist in the returning of updated genetic test results to clinics and patients. RESULTS: Novel clinically actionable pathogenic variants were identified in the PALB2 gene in 18 participants (0.6%), the majority of whom were recontacted with their new or updated genetic test results. Eight individuals were unable to be recontacted; five individuals had already learnt about their new or updated findings from genetic testing outside the context of this study; three individuals prompted cascade testing in family members; two individuals were deceased. CONCLUSION: Novel pathogenic variants in PALB2 were identified in 18 individuals through retrospective gene panel testing. Recontacting these individuals regarding these new or updated findings had a range of outcomes. The process of conveying genomic results within this framework can be effectively accomplished while upholding patient autonomy, potentially leading to advantageous outcomes for patients and their families.

[68Ga]Ga-FAP-2286, a novel promising theragnostic approach for PET/CT imaging in patients with various type of metastatic cancers.

BACKGROUND: Fibroblast activation protein (FAP) has emerged as a promising target for diagnosis and therapeutic intervention due to high expression and accumulation in the stromal compartments of a variety of malignant tumors. FAP-2286 utilizes cyclic peptides with FAP-binding characteristics to enhance the retention of the imaging agent within tumors, in contrast to the small-molecule FAP inhibitors (FAPI) like FAPI-04/46. The aim of this study was to quantify the tumor uptake of [68Ga] Gallium-FAP-2286 within primary solid tumors, adjacent excised tissues, and metastatic lesions. METHODS: In this prospective study, 21 patients (average age 51.9) with various diagnoses of remaining and metastatic cancers participated. Among them, six had metastatic sarcoma, and 14 had adenocarcinoma, including eight breast, two rectum, two lung, two pancreas, and one thyroid cases. The patients underwent a [68Ga]Ga-FAP-2286 PET/CT scan. An hour post-administration of [68Ga]Ga-FAP-2286, a visual assessment of whole body scans and semi-quantification of the PET/CT results were carried out. The standardized uptake values (SUV)max of [68Ga]Ga-FAP-2286 in tumor lesions and the tumor-to-background ratio (TBR) were then calculated. RESULTS: The vital signs of the patients, such as heart rate, blood pressure, and temperature, were observed before, during, and after the diagnostic procedure during the 4-h follow-up. All individuals underwent the [68Ga]Ga-FAP-2286 PET/CT scans without any signs of drug-associated pharmacological effects. The PET/CT scans displayed substantial absorption of [68Ga]Ga-FAP-2286 in tumor lesions in all patients (100% (21/21)). Irrespective of the tumors' origins (epithelial or mesothelium) and whether they exhibited local recurrence, distant recurrence, or metastatic lesions, the PET/CT scans revealed the uptake of [68Ga]Ga-FAP-2286 in these lesions. CONCLUSION: Overall, these data suggest that [68Ga]Ga-FAP-2286 is a promising FAP derivative for efficient metastatic cancer diagnosis and being considered as a potential compound for therapeutic application in patients with advanced metastatic cancers.

Her-2/neu gene amplification and its correlation with other prognostic factors in Iranian breast cancer patients.

BACKGROUND: Breast cancer is one of the most common diseases in females, arising from overexpression of a variety of oncogenes like HER2/neu. The amplification rate of this gene is variable in different breast cancer patients. In this study, the amplification of the HER2/neu oncogene was distinguished in breast cancer patients and its correlation with prognostic factors. Also, the simultaneous effect of prognostic factors on the occurrence of a specific prognostic factor was investigated. MATERIALS AND METHODS: The multiplex PCR technique was used to assay the amplification of the HER2/neu oncogene in breast cancer patients. After extracting DNA from 100 tumor tissue and 8 normal breast tissue samples, the amplification of the HER2/neu gene was distinguished by the co-amplification of a single-copy reference gene, γ-IFN, and the target gene HER2/neu in the PCR reaction and using the Gel analyzer software. SPSS 23 and STATA 9.1 software were used for statistical analysis. RESULTS: The HER2/neu gene was amplification in 30% of the tumor samples. The statistical analysis showed a statistically significant relationship between HER2/neu gene amplification and progesterone receptors. Amplification of the HER2/neu gene significantly increases the chance of lymph node involvement. Also, the amplification of this gene in tumors with histological grade II tissue is more than grade I. CONCLUSION: The amplification of the HER2/neu gene can be used as an independent prognostic factor in predicting lymph node involvement and histological grade in breast cancer patients.

Sexual function index adaptation for breast cancer patients (FSFI-BC)- translation and psychometric properties of Persian version.

BACKGROUND: Effective interventions to improve sexual dysfunction in breast cancer survivors need screening of these dysfunctions with a suitable instrument. The aim of present study was translation and identifying psychometric properties of Female Sexual Function Index - Adapted for Breast Cancer (FSFI-BC) which has been specifically developed for breast cancer survivors. METHOD: This methodological study was performed between February 2017 and October 2018. 200 breast cancer survivors in stage 1 or 2 who were selected through convenience sampling method, completed the questionnaire. Reliability was assessed by Cronbach's alfa and test re-test analysis and construct validity was performed through confirmatory (CFA) and exploratory factor analysis( EFA). RESULTS: Six factors were extracted in exploratory factor analysis (EFA). These factors explained 74.6% of the total variance in in NSA group and 0.821 in SA group. Reliability evaluation indicated high internal consistency and good test re-test reliability. Cronbach's alpha coefficient in all areas of the tool was above 0.7 (the lowest and the highest measures were 0.885 and 0.945, respectively), which is a good indicator for reliability of an instrument. Confirmatory factor analysis showed an acceptable fitness for seven factors of FSFI-BC questionnaire (Normed Fit Index or NFI = 0.9 for both groups, Comparative of Fit Index or CFI = 0.93 and 0.92, χ 2/df = 1.68 and 1.71 for SA(Sexually Active) and NSA(No Sexually Active) individuals, respectively) . CONCLUSION: Study findings suggest that Persian version of FSFI-BC is a suitable instrument for sexual dysfunction screening in breast cancer survivors.

Clinical characteristics and surgical outcomes in patients with superior oblique muscle palsy: a retrospective study on 1057 patients.

BACKGROUND: To evaluate the clinical findings of patients with SOP who underwent surgery. METHODS: This historical cohort study was performed on 1057 SOP patients managed with surgery in Farabi Hospital, Iran, from 2011 to 2022. RESULTS: There were 990 (93.7%) patients with unilateral SOP with the mean age of 21.8 ± 14.8 years. Of these, 715 patients (72.2%) were diagnosed with congenital SOP, and 275 patients (27.8%) had acquired SOP (P < 0.001). In contrast, 67 (6.3%) patients were diagnosed with bilateral SOP, with the mean age of 19.4 ± 15.6 years. Among these, 18 cases exhibited the masked type. The mean angle of vertical deviation in primary position at far in unilateral and bilateral cases was 15.6 ± 8.3 and 13.3 ± 9.1 △, respectively (P < 0.001). In unilateral cases, abnormal head posture (AHP) was detected in 847 (85.5%) patients and 12 (1.2%) had paradoxical AHP. Amblyopia was found in 89 (9.9%) unilateral and 7 (10.3%) bilateral cases. Solitary inferior oblique myectomy, was the most common surgery in both unilateral (n = 756, 77.1%) and bilateral (n = 35, 52.2%) patients. The second surgery was performed for 84 (8.6%) unilateral and 33 (49.3%) bilateral cases (P < 0.001). The prevalence of amblyopia and the mean angle of horizontal deviation were significantly higher in patients who needed more than one surgery (all P < 0.05). CONCLUSION: Congenital SOP was more than twice as frequent as acquired SOP and about 90% of unilateral and 50% of bilateral cases were managed with one surgery. Amblyopia and significant horizontal deviation were the most important factors for reoperation. TRIAL REGISTRATION: The Institutional Review Board approval was obtained from the Tehran University of Medical Sciences (IR.TUMS.FNM.REC.1400.012) and this study adhered to the tenets of the Declaration of Helsinki and HIPAA.

Strabismus management in retinoblastoma survivors.

PURPOSE: To report the result of strabismus surgery in eye-salvaged retinoblastoma (Rb) patients. METHODS: A retrospective case series including 18 patients with Rb and strabismus who underwent strabismus surgery after completing tumor treatment by a single pediatric ophthalmologist. RESULTS: A total of 18 patients (10 females and 8 males) were included with a mean age of 13.3 ± 3.0 (range, 2-39) months at the time tumor presentation and 6.0 ± 1.5 (range, 4-9) years at the time of strabismus surgery. Ten (56%) patients had unilateral and 8(44%) had bilateral involvement and the most common worse eye tumor's group was D (n = 11), C (n = 4), B (n = 2) and E (n = 1). Macula was involved by the tumors in 12 (67%) patients. The tumors were managed by intravenous chemotherapy (n = 8, 47%), intra-arterial chemotherapy (n = 7, 41%) and both (n = 3, 17%). After complete treatment, the average time to strabismus surgery was 29.9 ± 20.5 (range, 12-84) months. Except for one, visual acuity was equal or less than 1.0 logMAR (≤ 20/200) in the affected eye. Seven (39%) patients had exotropia, 11(61%) had esotropia (P = 0.346) and vertical deviation was found in 8 (48%) cases. The angle of deviation was 42.0 ± 10.4 (range, 30-60) prism diopter (PD) for esotropic and 35.7 ± 7.9 (range, 25-50) PD for exotropic patients (P = 0.32) that after surgery significantly decreased to 8.5 ± 5.3 PD in esotropic cases and 5.9 ± 6.7 PD in exotropic cases (P < 0.001). The mean follow-up after surgery was 15.2 ± 2.0 (range, 10-24) months, in which, 3 (17%) patients needed a second surgery. CONCLUSION: Strabismus surgery in treated Rb is safe and results of the surgeries are acceptable and close to the general population. There was not associated with tumor recurrence or metastasis.

Locoregional therapy containing surgery in metastatic breast cancer: Systematic review and meta-analysis.

INTRODUCTION: The role of locoregional therapy (LRT) containing surgery and systematic therapy in metastatic breast cancer patients remains controversial. This study investigated the effect of LRT in patients who were initially diagnosed with metastatic breast cancer (MBC) on overall survival (OS), locoregional progression-free survival (PFS), and distant systemic PFS. METHODS: The related keywords were searched in MEDLINE/PubMed, SCOPUS, and Web of Science databases up to August 15th, 2022. Hazard ratios (HR) with 95% confidence intervals (CIs) were pooled by the random-effects model. RESULTS: Seven articles with 1626 participants compared LRT with only systemic therapy (ST) for patients with de novo MBC. LRT did not improve (p = 0.28) OS compared to ST (HR: 0.83, 95% CI: 0.60, 1.16). LRT significantly improved locoregional PFS outcomes compared to ST (HR: 0.31, 95% CI: 0.15, 0.60, p = 0.001). LRT significantly (p = 0.001) improved OS in patients with solitary bone metastases (HR: 0.48; 95% CI: 0.35-0.67). CONCLUSION: LRT improves locoregional PFS. Furthermore, LRT improves OS in patients with solitary bone metastases.

DrugRep-HeSiaGraph: when heterogenous siamese neural network meets knowledge graphs for drug repurposing.

BACKGROUND: Drug repurposing is an approach that holds promise for identifying new therapeutic uses for existing drugs. Recently, knowledge graphs have emerged as significant tools for addressing the challenges of drug repurposing. However, there are still major issues with constructing and embedding knowledge graphs. RESULTS: This study proposes a two-step method called DrugRep-HeSiaGraph to address these challenges. The method integrates the drug-disease knowledge graph with the application of a heterogeneous siamese neural network. In the first step, a drug-disease knowledge graph named DDKG-V1 is constructed by defining new relationship types, and then numerical vector representations for the nodes are created using the distributional learning method. In the second step, a heterogeneous siamese neural network called HeSiaNet is applied to enrich the embedding of drugs and diseases by bringing them closer in a new unified latent space. Then, it predicts potential drug candidates for diseases. DrugRep-HeSiaGraph achieves impressive performance metrics, including an AUC-ROC of 91.16%, an AUC-PR of 90.32%, an accuracy of 84.63%, a BS of 0.119, and an MCC of 69.31%. CONCLUSION: We demonstrate the effectiveness of the proposed method in identifying potential drugs for COVID-19 as a case study. In addition, this study shows the role of dipeptidyl peptidase 4 (DPP-4) as a potential receptor for SARS-CoV-2 and the effectiveness of DPP-4 inhibitors in facing COVID-19. This highlights the practical application of the model in addressing real-world challenges in the field of drug repurposing. The code and data for DrugRep-HeSiaGraph are publicly available at https://github.com/CBRC-lab/DrugRep-HeSiaGraph .

A registration trend in eyelid skin cancers and associated risk factors in Iran, 2005-2016.

BACKGROUND: Eyelid skin cancers are the most prevalent ophthalmic malignancies. This study aimed to evaluate the association of the Human Development Index (HDI) and lifestyle risk factors with eyelid skin cancers in Iran. METHODS: This ecological study analyzed the data collected from the Iranian National Population-based Cancer Registry (2005-2016). The data on provincial-level eyelid skin cancer risk factors were obtained from national sources. The association between provincial HDI and lifestyle risk factors with the prevalence of eyelid skin cancers was assessed. RESULTS: The mean 12-year age-standardized incidence rate (ASIR) of eyelid skin cancers was 16.22 per 100,000 (9,104 cases). The overall ASIR showed an upward trend with an estimated annual average increase of 0.006 per year. There were positive correlations between the prevalence of overall eyelid skin cancers and provincial HDI, smoking, and obesity (r = 0.32, 0.42, and 0.37, respectively). In multivariate analysis, obesity/overweight remained a positive predictor for high prevalence of total eyelid skin cancers (OR = 1.97, 95%CI = 1.08-3.58, P = 0.026), carcinoma (2.10, 1.15-3.83, P = 0.015), and basal cell carcinoma (1.48, 0.99-2.20, P = 0.054). CONCLUSIONS: An increasing trend in ASIR of eyelid skin cancers was observed in more than a decade in Iran which was positively associated with provincial HDI and prevalence of obesity. The findings of the study highlight the importance of promotional programs for preventing obesity/overweight and appropriate allocation of screening facilities based on the HDI level.

Water Oxidation by a Copper(II) Complex with 6,6'-Dihydroxy-2,2'-Bipyridine Ligand: Challenges and an Alternative Mechanism.

Recently, copper(II) complexes have been extensively investigated as oxygen-evolution reaction (OER) catalysts through a water-oxidation reaction. Herein, new findings regarding OER in the presence of a Cu(II) complex with 6,6'-dihydroxy-2,2'-bipyridine ligand are reported. Using scanning electron microscopy, energy dispersive spectrometry, X-ray diffraction, Raman spectroscopy, in situ visible microscopy, in situ visible spectroelectrochemistry, X-ray absorption spectroscopy, and electrochemistry, it is hypothesized that the film formed on the electrode's surface in the presence of this complex causes an appropriated matrix to produce Cu (hydr)oxide. The resulting Cu (hydr)oxide could be a candidate for OER catalysis. The formed film could form Cu (hydr)oxide and stabilize it. Thus, OER activity increases in the presence of this complex.

DrugRep-KG: Toward Learning a Unified Latent Space for Drug Repurposing Using Knowledge Graphs.

Drug repurposing or repositioning (DR) refers to finding new therapeutic applications for existing drugs. Current computational DR methods face data representation and negative data sampling challenges. Although retrospective studies attempt to operate various representations, it is a crucial step for an accurate prediction to aggregate these features and bring the associations between drugs and diseases into a unified latent space. In addition, the number of unknown associations between drugs and diseases, which is considered negative data, is much higher than the number of known associations, or positive data, leading to an imbalanced dataset. In this regard, we propose the DrugRep-KG method, which applies a knowledge graph embedding approach for representing drugs and diseases, to address these challenges. Despite the typical DR methods that consider all unknown drug-disease associations as negative data, we select a subset of unknown associations, provided the disease occurs because of an adverse reaction to a drug. DrugRep-KG has been evaluated based on different settings and achieves an AUC-ROC (area under the receiver operating characteristic curve) of 90.83% and an AUC-PR (area under the precision-recall curve) of 90.10%, which are higher than in previous works. Besides, we checked the performance of our framework in finding potential drugs for coronavirus infection and skin-related diseases: contact dermatitis and atopic eczema. DrugRep-KG predicted beclomethasone for contact dermatitis, and fluorometholone, clocortolone, fluocinonide, and beclomethasone for atopic eczema, all of which have previously been proven to be effective in other studies. Fluorometholone for contact dermatitis is a novel suggestion by DrugRep-KG that should be validated experimentally. DrugRep-KG also predicted the associations between COVID-19 and potential treatments suggested by DrugBank, in addition to new drug candidates provided with experimental evidence. The data and code underlying this article are available at https://github.com/CBRC-lab/DrugRep-KG.

Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository.

BACKGROUND: This study aimed to identify and resolve discordant variant interpretations across clinical molecular genetic laboratories through the Canadian Open Genetics Repository (COGR), an online collaborative effort for variant sharing and interpretation. METHODS: Laboratories uploaded variant data to the Franklin Genoox platform. Reports were issued to each laboratory, summarising variants where conflicting classifications with another laboratory were noted. Laboratories could then reassess variants to resolve discordances. Discordance was calculated using a five-tier model (pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB), benign (B)), a three-tier model (LP/P are positive, VUS are inconclusive, LB/B are negative) and a two-tier model (LP/P are clinically actionable, VUS/LB/B are not). We compared the COGR classifications to automated classifications generated by Franklin. RESULTS: Twelve laboratories submitted classifications for 44 510 unique variants. 2419 variants (5.4%) were classified by two or more laboratories. From baseline to after reassessment, the number of discordant variants decreased from 833 (34.4% of variants reported by two or more laboratories) to 723 (29.9%) based on the five-tier model, 403 (16.7%) to 279 (11.5%) based on the three-tier model and 77 (3.2%) to 37 (1.5%) based on the two-tier model. Compared with the COGR classification, the automated Franklin classifications had 94.5% sensitivity and 96.6% specificity for identifying actionable (P or LP) variants. CONCLUSIONS: The COGR provides a standardised mechanism for laboratories to identify discordant variant interpretations and reduce discordance in genetic test result delivery. Such quality assurance programmes are important as genetic testing is implemented more widely in clinical care.

The effect of anamorelin (ONO-7643) on cachexia in cancer patients: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cachexia is associated with increased morbidity and mortality rates in patients with cancer. This meta-analysis aims to explore the effect of anamorelin on cancer cachexia markers. METHODS: We searched MEDLINE/PubMed, SCOPUS, and WOS from their inception until 5 June 2022. A systematic search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We included trials investigating the effect of anamorelin on body weight, lean body mass, fat mass, insulin-like growth factor 1 (IGF-1), handgrip, quality of life insulin-like growth factor-binding protein 3 (IGFBP-3), and in patients with cancer. A random-effects model was run to pooled results. RESULTS: Five articles providing 1331 participants were analyzed in this study. Pooled analysis revealed a significant increase in body weight (weighted mean difference (WMD): 1.56 kg, 95% confidence interval (CI): 1.20, 1.92; I2= 0%), lean body mass (WMD: 1.36 kg, 95% CI: 0.85, 1.86; I2= 53.1%), fat mass (WMD: 1.02 kg, 95% CI: 0.51, 1.53; I2= 60.7%), IGF-1 (WMD: 51.16 ng/mL, 95% CI: 41.42, 60.90, I2= 0%), and IGFBP-3 (WMD: 0.43 µg/mL, 95% CI: 0.17, 0.68, I2= 98.6%). Results showed no significant increase in appetite when analysis run on all studies without considering different doses 0.29 (95% CI: -0.30, 0.89, I2= 73.8%), however, there was a significant increase in appetite without heterogeneity and inconsistency 0.59 (95% CI: 0.32, 0.86; I2= 0%) in the 100 mg/day group compared to anamorelin non-user. CONCLUSIONS: Patients with cancer who receive anamorelin as a treatment for cachexia showed a significant increase in body weight, lean body mass, fat mass, IGF-1, and IGFBP-3.

The association of dietary antioxidant index (DAI) with breast cancer among Iranian women.

Recent studies have reported that dietary antioxidants can influence the risk of breast cancer (BC). Therefore, this study aimed to investigate the association of dietary antioxidant index (DAI) with BC among Iranian women. This case-control study was conducted on 180 women with breast cancer and 360 healthy women who were referred to the cancer clinic of Shohadaye Tajrish Hospital in Tehran, Iran. A 168-item validated food frequency questionnaire (FFQ) was used to assess dietary intake. The DAI score was calculated based on the intake of antioxidant vitamins and minerals derived from the FFQ. The control group had a significantly higher intake of vitamin D (1.79±1.56 vs. 1.05±0.84 µg/d; P=0.01) and lower intake of calorie (2315±1066 vs. 2737±925 kcal/d; P=0.01), carbohydrate (311±170 vs. 402±124 g/d; P=0.01), iron (15.4±12.1 vs. 19.7±6.4 mg/d; P=0.01), thiamine (1.5±0.7 vs. 2.3±0.9 mg/d; P=0.01), niacin (18.2±9.2 vs. 24.3±7.9 mg/d; P=0.01), folic acid (465±308.7 vs. 673±205.2 µg/d; P=0.01), and selenium (82.6±41.7 vs. 98.7±40.8 µg/d; P=0.01) compared to the case group. No significant association was found between DAI with breast cancer after adjustments for age. DAI had a negative association with breast cancer after additional adjustments for BMI, the number of pregnancies, duration of breastfeeding, menopause age, and total energy intake (OR: 0.91, 95% CI: 0.90-.93, and all P<0.001). The present study identified a negative association between DAI and the risk of BC, indicating the importance of antioxidants in preventing BC. Longitudinal studies should be conducted to confirm this association.

Evaluating the Utility of ctDNA in Detecting Residual Cancer and Predicting Recurrence in Patients with Serous Ovarian Cancer.

Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any cancer cells left in the peritoneal cavity after treatment may precipitate a cancer recurrence. In many cases, these cells are occult and are not visible to the surgeon. Analysis of circulating tumour DNA in the blood (ctDNA) may offer a sensitive method to predict the presence of occult (non-visible) residual disease after surgery and may help predict disease recurrence. We assessed 48 women diagnosed with serous ovarian cancer (47 high-grade and 1 low-grade) for visible residual disease and for ctDNA. Plasma, formalin-fixed paraffin-embedded (FFPE) tumour tissue and white blood cells were used to extract circulating free DNA (cfDNA), tumour DNA and germline DNA, respectively. We sequenced DNA samples for 59 breast and ovarian cancer driver genes. The plasma sample was collected after surgery and before initiating chemotherapy. We compared survival in women with no residual disease, with and without a positive plasma ctDNA test. We found tumour-specific variants (TSVs) in cancer cells from 47 patients, and these variants were sought in ctDNA in their post-surgery plasma. Fifteen (31.9%) of the 47 patients had visible residual disease; of these, all 15 had detectable ctDNA. Thirty-one patients (65.9%) had no visible residual disease; of these, 24 (77.4%) patients had detectable ctDNA. Of the patients with no visible residual disease, those patients with detectable ctDNA had higher mortality (20 of 27 died) than those without detectable ctDNA (3 of 7 died) (HR 2.32; 95% CI: 0.67-8.05), although this difference was not statistically significant (p = 0.18). ctDNA in post-surgical serum samples may predict the presence of microscopic residual disease and may be a predictor of recurrence among women with ovarian cancer. Larger studies are necessary to validate these findings.

The Role of the Health Belief Model in Explaining Why Symptomatic Iranian Women Hesitate to Seek Early Screening for Breast Cancer: a Qualitative Study.

Early detection of breast cancer (BC) is important to increase the likelihood of treatment and improve the quality of life and survival. The study explored why symptomatic women linger to seek early screening for BC diagnosis based on the health belief model (HBM). In this qualitative study, 20 participants were selected using the purposive sampling method (9 health professionals and 11 female patients BC). Data were collected using in-depth, semi-structured interviews in 2019. Transcribed interview data were analyzed using the directed content analysis informed by HBM. According to the participants' experiences, although most patients comprehended the extent of the disease, they did not see themselves at risk of BC. Some were not adequately aware of the benefits of early diagnosis and did not have the self-efficacy required for early presentation. The main barriers to the early presentation included lack of awareness, financial problems, embarrassment over the clinical examination, and inadequate access to specialized centers. According to HBM, while designing and implementing educational programs, it is recommended to focus on reinforcing perceived susceptibility, perceived benefits, and perceived self-efficacy, providing access to facilities, and removing possible barriers and cultural issues to encourage women for timely referral for BC screening.

Combined anticancer effects of simvastatin and arsenic trioxide on prostate cancer cell lines via downregulation of the VEGF and OPN isoforms genes.

Arsenic trioxide (ATO) and statins have been demonstrated to have anti-neoplastic properties; however, the data regarding their combination therapy is limited. Thus, we aimed to study the effects of ATO, Simvastatin and their combination in proliferation, apoptosis and pathological angiogenesis in prostate cancer cell lines. The human prostate cell lines were treated with different concentrations of Simvastatin and ATO alone and combined to find effective doses and IC50 values. In addition, the percentage of apoptotic cells was evaluated by annexin/PI staining, and mRNA expression levels of the apoptotic gene, including OPN isoforms and VEGF, were investigated using real-time PCR. Our data displayed that Simvastatin (12 and 8 µM in PC3 and LNCaP cell lines respectively), ATO (8 and 5 µM in PC3 and LNCaP cell lines respectively), and also their combination (12 µM Simvastatin and 8 µM ATO in PC3, 8 µM Simvastatin and 5 µM ATO in LNCaP cell lines respectively) significantly increased the percentage of apoptotic cells. Also, we showed that the combination therapy by Simvastatin and ATO increased cell apoptosis and inhibited cell proliferation, providing anti-proliferative and anti-angiogenic properties, possibly via downregulation of the expression of VEGF and OPN genes. These results provide new perceptions regarding the anticancer roles of ATO and statins' combination therapy in prostate cancer.

The effects of FTO gene rs9939609 polymorphism on the association between breast cancer and dietary intake.

Breast cancer (BC) is the leading cause of cancer-related deaths in females worldwide and is related to genetic and environmental factors. Dietary components may strongly influence the risk of BC. A possible association was also reported between the fat mass and obesity-associated (FTO) single-nucleotide polymorphisms (SNPs) and BC. This study aimed to investigate the impact of FTO rs9939609 polymorphism on the association between BC and dietary intake. This study was conducted on 180 women with BC as the case group and 360 healthy women as the control group. The dietary intakes were assessed by a valid 168-item food frequency questionnaire (FFQ). The FTO gene was genotyped for rs9939609 polymorphism. After adjusting the confounding variables, there was no significant association between dietary intake and BC in individuals without risk allele. A positive association between dietary intake of omega-6 fatty acids and BC was found only in individuals with risk allele of FTO gene (OR: 1.31, 95% CI: 1.08-1.60, p: 0.006). FTO gene risk allele may influence the effect of diet on breast cancer risk. Further studies are needed to assess the possible effects of the FTO genotype on the association between BC risk and dietary components.