Cancer Research Articles

Environmental stressors experienced by cancer patients and caregivers shaped their attitudes and perceptions towards climate change in Puerto Rico.

Environmental stressors experienced by cancer patients and caregivers shaped their attitudes and perceptions towards climate change in Puerto Rico.

The Alteration Level of VEGF of Colon Cancer Cell After Induction with Mandarin Orange (<i>Citrus Reticulata</i>) Peel Ethanol Extract

The natural ingredient-based therapy extracted from various plants is assumed more tolerable to cancer patients’ bodies than synthetic drugs. To tell successful novel cancer therapy, an indicator is needed to confirm the result. VEGF is a pro-angiogenic factor that leads the cancer cells’ invasion to another organ and is associated with high mortality in patients. Hence, the VEGF level is widely used as one of the successful cancer therapy indicators. Purposed of research elucidated the effect of Mandarin orange peel ethanol extract (EEKJM) to improve the reduction of VEGF levels in colon cancer in vitro. This study was an experimental posttest and control group design to analyze different level of VEGF on cancer cells at end of the study. Research began with the preparation of EEKJM followed by a cytotoxic extract test using the MTT assay method. Furthermore, the measurement of VEGF levels by the VEGF ELISA kit protocol. One Way ANOVA was performed to analyze data.Results showed the cytotoxic test of the EEKJM and doxorubicin against WiDr cells was 240 g/ml and 1.59 µg/ml. VEGF levels showed decreasing after being induced with EEKJM and doxorubicin with doses ½ IC50 and ¼ IC50. Conclusion: EEKJM was able to reduce VEGF levels and viability of WiDr colon cancer cells. The advantages are as much as initial evidence of the ability of the orange to treat cancer even though further animal studies or evidence of a pathway of decrease of the VEGF or other signals are required.

Chinese expert consensus on diagnosis and treatment of pulmonary nodules(2024)

Lung cancer is the leading cause of the incidence and mortality of malignant tumors in China. The 5-year survival rate released for China in 2018 was 19.7%. The 5-year survival rate for stage Ⅰ patients is 77%-92%. Early diagnosis and treatment of lung cancer are key to improving the 5-year overall survival rate and prognosis of lung cancer patients. Therefore, experts from the Academic Group of Lung Cancer in Chinese Thoracic Society and Chinese Alliance Against Lung Cancer Expert Group formulated the Chinese Expert Consensus on the Diagnosis and Treatment of Lung Nodules in 2015 to standardize the diagnosis and treatment of lung nodules. In 2018, this consensus was updated to formulate the Chinese Expert Consensus on Diagnosis and Treatment of Lung Nodules (2018 edition), and widely applied in multiple branch centers of Chinese Alliance Against Lung Cancer, proposing the Intelligent Treatment of Million Early Lung Cancer Project. Based on applied experience of the expert consensus in recent years, with reference to the latest evidence has been updated, Chinese Expert Consensus on Diagnosis and Treatment of Lung Nodules (2024 edition) was formulated. The updated content of this consensus mainly includes the following aspects: (1) Define the screening age of high-risk lung cancer populations in China based on the national conditions; (2) Propose definition of "difficult-to-determine pulmonary nodules" to avoid delaying the diagnosis and treatment; (3) Evaluate pulmonary nodules assisted by artificial intelligence (AI) imaging-assisted diagnostic system and propose human-machine MDT to avoid the limitations of AI; (4) Evaluate pulmonary nodules by routine and individualized evaluations for different populations, and make recommendations based on evidence-based management guidelines for different types and sizes of pulmonary nodules. In the updated consensus, 18 consensus points were recommended as a reference for clinical management of pulmonary nodules to improve the 5-year overall survival rate and the prognosis of lung cancer in China.

Ocular surface adverse reactions of antitumor-targeted drugs

With the extensive application of targeted drugs, the survival rate of cancer patients has been significantly improved. However, adverse reactions to the drugs have also become apparent, especially those affecting the ocular surface, which can severely impact patients' vision and quality of life. The article systematically analyzes a variety of targeted drugs, including epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, fibroblast growth factor receptor inhibitors, selective estrogen receptor modulators, vascular endothelial growth factor receptor inhibitors, aromatase inhibitors, proteasome inhibitors, antibody-drug conjugates, Bruton's tyrosine kinase inhibitors, FMS-like tyrosine kinase 3 inhibitors, and cyclin-dependent kinase inhibitors, and discusses their adverse reactions on the ocular surface. The review emphasizes the role of clinicians in monitoring and managing patients' ocular surface health and the importance of early diagnosis and intervention to ensure that patients receive optimal visual protection while undergoing antitumor treatment.

The Construction of Peer Support Among Recently Diagnosed Breast Cancer Patients.

Breast cancer (BC) and its treatments decrease patients' psychological well-being. Peer support is one form of social support, but little is known about what gives rise to peer support. The purpose of this study was to examine how peer support is constructed among recently diagnosed BC patients. Eighteen women were randomly picked from 130 women who had received phone calls from a trained peer supporter and were invited to group interviews. In the interviews, patients discussed their cancer, peer support experiences, and social support. The transcribed data were analyzed using Braun and Clarke's thematic analysis approach. The construction of peer support among newly diagnosed BC patients was complex. It depended on the needs of the patient and the success of interactions. Once they had received a diagnosis, the lives of the patients changed suddenly, and patients dove into the I-we-others consideration and had a need to talk. Interaction with peer supporters gave them a chance to share their stories. At their best, interactions led to belonging, caring, and a sense of security. The need to be heard and seen is strong in a patient's changing health situation. Peer support plays an important role in high-standard care and in strengthening patients' self-determination. Hospitals should create chances for supportive communication, and the supportive communication should be easily accessible and successful. The training of peer supporters should ensure that they have reflected on their own BC process and know how to consider the needs of newly diagnosed patients.

Association between BMI and success of transaxillary venous port implantation: A retrospective cohort study.

Totally implanted venous access device are widely used for long-term chemotherapy in cancer patients. Previous studies have only focused on the analysis of complications associated with infusion port implantation, ignoring the causes of unsuccessful infusion port implantation. The purpose of this study was to investigate the association between body mass index (BMI) and the success rate of transaxillary intravenous port implantation in breast cancer patients. To review 361 breast cancer patients who underwent intravenous port implantation from January 2021 to September 2021. Baseline data, and surgical data were collected from the patients, and the success rate of puncture of the axillary vein was recorded. The logistic regression analysis and smoothed curve fitting were used to assess the relationship between BMI and the success rate of axillary venipuncture. In addition, subgroup analyses were performed to explore potential interactions. Under ultrasound guidance, 67.3% of patients (243/361) had an infusion port implanted by axillary vein puncture. There was a roughly linear relationship between BMI and the success rate of axillary venipuncture. In the multiple regression equation, BMI was significantly and negatively associated with the success rate of axillary venipuncture (OR = 0.83; 95% CI = 0.77-0.89; p < 0.001). Stratified analysis showed that the relationship between BMI and the success rate of axillary venipuncture was stable and unaffected by other variables. The higher the patient's BMI, the higher the chance of difficult axillary venipuncture or failed cannulation.

Sjogren's syndrome due to immune checkpoint inhibitors (ICIs): Insights from a single-institution series and systematic review of the literature.

Careful adverse event assessment and management are important when prescribing immune checkpoint inhibitors (ICIs) to cancer patients. Iatrogenic Sjogren's syndrome is a relatively rare immune-related adverse event (irAEs) that affects the moisture-producing glands. We describe a series of four patients who developed Sjogren's syndrome while being treated with ICIs at a community cancer center in Southern California, USA (1/1/2017-12/31/2023). Patient, drug and disease-related data were collected by retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases in the literature (1/1/2016-12/31//2023). Of 224 cancer patients at our center treated with ICIs, four (1.8%) developed iatrogenic Sjogren's syndrome. All of our patients were male; three received PD-1 inhibitors (nivolumab, pembrolizumab) and one received the PD-L1 inhibitor atezolizumab. The median time to development of Sjogren's syndrome was 24 weeks (range, 8-36 weeks); dry mouth symptoms were more prominent than dry eye symptoms. None of the patients had elevated SS-A, SS-B or antinuclear antibodies. One patient developed multiple tooth cavities and had several extractions, due to severe xerostomia. Management of all patients was primarily symptomatic. Two cases were irreversible; one was reversible and the 4th case is undermined as he is still on ICI therapy. Our systematic review of the literature identified 80 cases in five articles. Incidence of xerostomia was twice of that of xerophthalmia. The male/female ratio was 1.5:1. SS-A, SS-B, or antinuclear antibodies were found in only 9% of patients. Steroids were reported to have had only a limited role in management. The incidence of Sjogren's syndrome due to ICIs in our center was 1.8%. Details of clinical course and management in these patients are presented. Caring for patients with ICI-related Sjogren's syndrome is facilitated by a multidisciplinary effort including oncologists, otolaryngologists, dentists, ophthalmologists and rheumatologists. Expanding the knowledge base pertaining to iatrogenic Sjogren's syndrome in patients on ICIs will be helpful in promoting early detection and treatment, and improving outcomes.

Adverse Social Determinants of Health Elevate Uncontrolled Hypertension Risk: A Cardio-Oncology Prospective Cohort Study.

The role of social determinants of health (SDOH) in controlling hypertension (HTN) in cancer patients is unknown. We hypothesize that high SDOH scores correlate with uncontrolled HTN in hypertensive cancer patients. In our prospective study patients completed the PRAPARE questionnaire. After integrating home and clinic blood pressure readings, uncontrolled HTN was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg. Using Cox regression, we analyzed the impact of SDOH on HTN control, adjusting for relevant factors. The study involved 318 participants (median age 66.4, median follow-up 166 days, SDOH score 6.5 ± 3.2), with stress, educational insecurity, and social isolation as prevalent adverse SDOH. High SDOH scores led to 77% increased risk of uncontrolled HTN (aHR 1.77; 95% CI 1.10-2.83, p = .018). Urban residents with high SDOH scores were at an even greater risk. Identifying SDOH and mitigating underlying factors may help control HTN, the most typical disease process treated in all cardio-oncology clinics.

Clinical efficacy and safety of immune checkpoint inhibitors plus anlotinib as secondline or subsequent therapy in extensive stage small cell lung cancer: a retrospective study.

Treatments are limited for extensive stage small cell lung cancer (ES-SCLC) patients in secondline or subsequent setting. This study aimed to explore the clinical efficacy and safety of immune checkpoint inhibitors (ICIs) plus anlotinib as secondline or subsequent therapy in ES-SCLC. We retrospectively analyzed 116 patients with ES-SCLC at Shandong Provincial Qianfoshan Hospital between January 2019 and March 2024. According to the different therapy regimes, they were divided into three groups, ICI plus anlotinib as secondline or subsequent therapy group (ICI + anlotinib group), single ICI as secondline or subsequent therapy group (single ICI therapy group), single chemotherapy as secondline therapy group (single chemotherapy group). Kaplan-Meier method was used to compare the progression-free survival (PFS) and the overall survival time (OS) among these three groups. Cox regression analysis was used to analyze different factors which correlated to PFS and OS. The adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Kaplan-Meier analysis showed that patients in ICI + anlotinib group had a longer PFS and OS compared to patients in single ICI therapy group (median PFS [mPFS]: 6.7months vs. 4.6months, P = 0.007; median OS [mOS]:12.4months vs. 8.4months, P = 0.041) and single chemotherapy group (mPFS: 6.7months vs. 3.0months, P < 0.001; mOS: 12.4months vs. 7.2months, P = 0.002). The Cox regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), liver metastasis, brain metastasis and treatment regimes were independent predictors that affecting the PFS and OS of all the enrolled patients. The common adverse events (AEs) were wleukopenia and fatigue. There was no significant statistical difference in other AEs among the three groups except for leukopenia. ICI + anlotinib as secondline or subsequent therapy has better efficacy than single ICI group and single chemotherapy group and with tolerable toxicities for patients with ES-SCLC.

Loss of STK11 Suppresses Lipid Metabolism and Attenuates KRAS-Induced Immunogenicity in Patients with Non-Small Cell Lung Cancer.

As many as 30% of non-small cell lung cancer (NSCLC) patients harbor oncogenic KRAS mutations, which lead to extensive remodeling of the tumor immune microenvironment. Though co-mutations in several genes have prognostic relevance in KRAS-mutated patients, their effect on tumor immunogenicity are poorly understood. In the present study, a total of 189 NSCLC patients underwent a standardized analysis including immunohistochemistry, whole exome DNA sequencing, and whole transcriptome RNA sequencing. Patients with activating KRAS mutations demonstrated a significant increase in PD-L1 expression and CD8+ T-cell infiltration. Both were increased in the presence of a co-occurring TP53 mutation and lost with STK11 co-mutation. Subsequent genomic analysis demonstrated that KRAS/TP53 co-mutated tumors had a significant decrease in the expression of glycolysis-associated genes, and increase in several genes involved in lipid metabolism, notably Lipoprotein Lipase (LPL), Low Density Lipoprotein Receptor (LDLR), and LDLRAD4. Conversely, in the immune-excluded KRAS/STK11 co-mutated group, we observed diminished lipid metabolism and no change in anaerobic glycolysis. Interestingly, in patients with low expression of LPL, LDLR, or LDLRAD4, KRAS mutations had no effect on tumor immunogenicity. However, in patients with robust expression of these genes, KRAS mutations were associated with increased immunogenicity and associated with improved overall survival. Our data further suggest that the loss of STK11 may function as a metabolic switch, suppressing lipid metabolism in favor of glycolysis, thereby negating KRAS-induced immunogenicity. Hence, this concept warrants continued exploration, both as a predictive biomarker and potential target for therapy in patients receiving ICI-based immunotherapy.

Abiraterone, Olaparib, or Abiraterone + Olaparib in First-line Metastatic Castration-Resistant Prostate Cancer with DNA Repair Defects (BRCAAway).

Deleterious germline/somatic homologous recombination-repair mutations (HRRm) are present in ~25% of metastatic castration resistant prostate cancer (mCRPC) patients. Preclinically, PARP-Inhibition demonstrated synergism with ARP-targeted therapy. This trial evaluated efficacy of ARP-Inhibitor versus PARP-Inhibitor versus combination as first-line therapy in mCRPC patients with HRRm. BRCAAway is a biomarker pre-selected, randomized, phase-2 trial. Patients with BRCA1/2 and/or ATM alterations were randomized 1:1:1 to Arm1: Abiraterone (1000mg)/prednisone (Abi/pred) (5mg), Arm2: Olaparib (Ola) (300mg), or Arm3: Abiraterone/prednisone + Olaparib (Abi/pred+Ola). Single-agent arms could cross over at progression. Exploratory Arm4 patients with other HRRm received Olaparib alone. The primary endpoint was progression-free survival (PFS), and secondary endpoints were objective response, PSA response, and safety. 61/165 eligible patients had BRCA1/2 or ATM mutations: Median age: 67 (IQR 62-73) years. Mutations: BRCA1 n=3, BRCA2 n=46, ATM n=11, multiple n= 1; 33 germline, 28 somatic. Median PFS (95% CI): Abi/pred, 8.6 months (m) (2.9, 17), Ola, 14 m (8.4, 20), Abi/pred+Ola, 39 m (22, NR). There were no G4/5 AEs. 8/19 on Abi/pred crossed over to Ola, and 8/21 vice versa: Median PFS (95% CI) from crossover: Ola-after-Abi/pred, 8.3 m (5.5, 15); Abi/pred-after-Ola, 7.2 m (2.8, NR). Median PFS (95% CI) from randomization: Ola-after-Abi/pred, 16 m (7.8, 25), Abi/pred-after-Ola, 16 m (11, NR). 17/165 patients with other HRRm received olaparib: Median PFS (95% CI): 5.5 m (2, 11). In mCRPC patients with BRCA1/2 or ATM HRRm, abiraterone/prednisone + olaparib was well tolerated and demonstrated longer PFS versus either agent alone or sequentially.

Benefit of adjuvant chemotherapy on recurrence free survival per consensus molecular subtype in stage III colon cancer.

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018. Patients treated with and without adjuvant chemotherapy were matched based on tumor location, T- and N-stage (n = 522). Tumor material was available for 464 patients, with successful RNA extraction and CMS subtyping achieved in 390 patients (surgery alone group: 192, adjuvant chemotherapy group: 198). In the overall cohort, CMS4 was associated with poorest prognosis (HR 1.55; p = .03). Multivariate analysis revealed favorable RFS for the adjuvant chemotherapy group in CMS1, CMS2, and CMS4 tumors (HR 0.19; p = .01, HR 0.27; p < .01, HR 0.19; p < .01, respectively), while no significant difference between treatment groups was observed within CMS3 (HR 0.68; p = .51). CMS subtyping in this non-randomized cohort identified patients with poor prognosis and patients who may not benefit significantly from adjuvant chemotherapy.

MYBL2 Drives Prostate Cancer Plasticity: Inhibiting its Transcriptional Target CDK2 for RB1-Deficient Neuroendocrine Prostate Cancer.

Phenotypic plasticity is a recognized mechanism driving therapeutic resistance in prostate cancer (PCa) patients. While underlying molecular causations driving phenotypic plasticity have been identified, therapeutic success is yet to be achieved. To identify putative master regulator transcription factors (MR-TF) driving phenotypic plasticity in PCa, this work utilized a multiomic approach using genetically engineered mouse models of prostate cancer combined with patient data to identify MYBL2 as a significantly enriched transcription factor in PCa exhibiting phenotypic plasticity. Genetic inhibition of Mybl2 using independent murine PCa cell lines representing phenotypic plasticity demonstrated Mybl2 loss significantly decreased in vivo growth as well as cell fitness and repressed gene expression signatures involved in pluripotency and stemness. Because MYBL2 is currently not druggable, a MYBL2 gene signature was employed to identify cyclin-dependent kinase-2 (CDK2) as a potential therapeutic target. CDK2 inhibition phenocopied genetic loss of Mybl2 and significantly decreased in vivo tumor growth associated with enrichment of DNA damage. Together, this work demonstrates MYBL2 as an important MR-TF driving phenotypic plasticity in PCa. Further, high MYBL2 activity identifies PCa that would be responsive to CDK2 inhibition.

Do we need a re-TUR after en bloc resection of T1 stage bladder cancer?

A second look trans-urethral resection of the bladder (re-TUR) is recommended after the diagnosis of T1 high grade (T1HG) bladder cancer. Few studies have evaluated the results of re-TUR after a first en bloc resection (EBR) and none of them have specifically reported the pathological results on the field of previous T1 disease. To report the rate of upstaging and the rate of residual disease (RD) on the field of T1HG lesions resected with EBR. Between 01/2014 and 06/2022, patients from 2 centers who had a re-TUR after an EBR for T1HG urothelial carcinoma were retrospectively included. Primary endpoint was the rate of RD including the rate of upstaging to T2 disease on the scar of the primary resection. Secondary endpoints were the rate of any residual disease outside the field. Seventy-five patients were included. No muscle invasive bladder cancer lesions were found after re-TUR. Among the 16 patients who had a RD, 4 were on the resection scar. All of these lesions were papillary and high grade. RD outside the field of the first EBR was observed in 12 patients. After EBR of T1HG disease, none of our patients had an upstaging to MIBC. However, the rate of RD either on and outside the field of the EBR remains quite significant. We suggested that predictive factors of residual papillary disease (number of tumors at the initial TUR and concomitant CIS) might be suitable to select patient who will benefit of the re-TUR.

Comprehensive single-cell analysis deciphered microenvironmental dynamics and immune regulator olfactomedin 4 in pathogenesis of gallbladder cancer

ObjectiveElucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention.DesignWe performed single-cell transcriptome analysis on 230...

Illness perception and family resilience in gynaecologic cancer patients: A study on the mediating role of hope.

To investigate the level of family resilience among patients with gynaecologic cancer and explore hope as a mediator between perceptions of illness and family resilience. A cross-sectional study. From May to October 2022, researchers used convenience sampling to survey 320 patients with gynaecological cancer at a level 3A hospital in Jinan City. The study instruments included the General Information Questionnaire, Family Hardiness Index, Brief Illness Perception Questionnaire, and Herth Hope Index. SPSS 26.0 was used to analyse the mediation effect of hope. The mean score for family resilience was 55.86 ± 8.62. Illness perception was negatively associated with family resilience, while hope was positively associated with it. Additionally, hope mediated the relationship between illness perception and family resilience. There is considerable room for improvement in family resilience among patients with gynaecologic cancer. Interventions aimed at increasing hope can enhance family resilience. Healthcare providers can boost family resilience by fostering hope in patients, thereby promoting effective coping and adaptation to cancer. Patients primarily completed the questionnaires, providing insights into the factors that hindered and facilitated the development of family resilience. These findings were communicated to caregivers for further understanding and action.

Impact of Preoperative Time Intervals for Neoadjuvant Chemoradiotherapy on Short-term Postoperative Outcomes of Esophageal Cancer Surgery: A Population-Based Study Using the Dutch Upper Gastrointestinal Cancer Audit (DUCA) Data.

To clarify the impact of the preoperative time intervals on short-term postoperative and pathological outcomes in esophageal cancer patients who underwent neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. The impact of preoperative intervals on esophageal cancer patients who received multimodality treatment remains unknown. Patients(cT1-4aN0-3M0) treated with nCRT plus esophagectomy were included using the Dutch national DUCA-database. Multivariate logistic regression was used to determine the effect of different time intervals upon short-term postoperative and pathological outcomes: diagnosis-to-nCRT intervals (≤5, 5-8 and 8-12wk), nCRT-to-surgery intervals (5-11, 11-17 and >17wk) and total preoperative intervals (≤16, 16-25 and >25wk). Between 2010-2021, a total of 5052 patients were included. Compared to diagnosis-to-nCRT interval ≤5 weeks, the interval 8-12 weeks was associated with higher risk of overall complications (P=0.049). Compared to nCRT-to-surgery interval 5-11 weeks, the longer intervals (11-17wk and >17wk) were associated with higher risk of overall complications (P-value=0.016; P-value<0.001) and anastomotic leakage (P-value=0.004; P-value=0.030), but the interval >17 weeks was associated with lower risk of ypN+ (P-value=0.021). The longer total preoperative intervals were not associated with the risk of 30-day mortality and complications compared to the interval ≤16 weeks, but the longer total preoperative interval (>25wk) was associated with higher ypT stage (P-value=0.010) and lower pCR rate (P-value=0.013). In patients with esophageal cancer undergoing nCRT and esophagectomy, prolonged preoperative time intervals may lead to higher morbidity and disease progression, and the causal relationship requires further confirmation.

A novel prognostic score (HAMP) for head and neck cancer patients with single and multiple SBRT-treated lung metastases derived from retrospective analyses of survival outcome.

We report on the characterization and introduction of a novel prognostic score for patients undergoing stereotactic body radiotherapy (SBRT) for the treatment of single and multiple pulmonary metastases (PMs) derived from head and neck cancer (HNC). In this retrospective study, we examined selected factors associated with progression-free survival (PFS) and overall survival (OS) among 59 patients with HNC treated with SBRT for a total of 118 PMs, between 2009 and 2023. Factors related to survival were included in the prognostic scoring system. Prognostic factors including histology, age, number of metastases, and performance status at first SBRT were weighted differently depending on the strength of correlation to PFS and OS. Total prognostic scores (HAMP) ranged from 13 to 24 points, with a cut-off total score of ≤18 scoring points for patients in a high-risk (HR) subcohort, and of ≥19 scoring points for patients in a low-risk group (LR). Median PFS (23.8 vs. 5.5 months, p < 0.001) and OS (61.3 vs. 16.4 months, p < 0.001) were significantly longer in the low-risk group compared to the high-risk group. The HAMP score might be a convenient tool to facilitate individualized treatment decisions and appropriate follow-up. The accuracy and reliability of the score requires further evaluation in prospective studies.

XRCC1 and XPD polymorphisms: clinical outcomes and risk of prostate cancer in Bangladeshi population.

In Bangladesh, only a fraction of prostate cancer patients are diagnosed annually due to lack of symptom awareness and screening challenges, resulting in high mortality. Aiming to improve screening methods, we evaluated X-ray cross-complementing gene 1 (XRCC1) Arg194Gln and Xeroderma pigmentosum group D (XPD) Lys751Gln polymorphisms to determine their relevance as potential markers for predicting prostate cancer risk, severity and clinical parameters in Bangladeshi population. This study included 132 prostate cancer patients and 135 healthy controls. Genotype analysis was done from blood samples by the PCR-RFLP method. The XRCC1 Trp/Trp genotype was associated with prostate cancer (ORadj = 5.51; 95% CI = 1.13-26.78; p-value = 0.03) compared to Arg/Arg genotype. No significant association was found between the XPD variants and prostate cancer risk. The XRCC1 Trp/Trp genotype increased prostate cancer risk in smokers and non-smokers but was statistically non-significant. In individuals without a family history of cancer, the XRCC1 Trp/Trp genotype had a non-significant 4.64-fold higher risk (ORadj=4.64; 95% CI = 0.88-24.36; p-value = 0.07), while the XPD Gln/Gln had a 2.66-fold non-significant higher risk (ORadj=2.66; 95% CI = 0.88-8.10; p-value = 0.09). The XRCC1 Trp/Trp variant was associated with hematuria risk, higher mean serum creatinine, and mean prostate-specific antigen (PSA) levels in prostate cancer patients. The XPD Gln/Gln variant was only associated with higher mean serum creatinine levels. Our findings suggest that XRCC1 screening may be used as a biomarker for prostate cancer to improve early diagnosis in Bangladesh.

Prostate cancer with BRCA2 pathogenic mutation: a clinicopathological analysis

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation (P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation (P=0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.