Cancer Research Malaysia

A substantial portion of the genetic predisposition for breast cancer is explained by multiple common genetic variants of relatively small effect. A subset of these variants, which have been identified mostly in individuals of European (EUR) and Asian ancestries, have been combined to construct a polygenic risk score (PRS) to predict breast cancer risk, but the prediction accuracy of existing PRSs in Hispanic/Latinx individuals (H/L) remain relatively low. We assessed the performance of several existing PRS panels with and without addition of H/L-specific variants among self-reported H/L women.

PRS performance was evaluated using multivariable logistic regression and the area under the ROC curve.

Both EUR and Asian PRSs performed worse in H/L samples compared with original reports. The best EUR PRS performed better than the best Asian PRS in pooled H/L samples. EUR PRSs had decreased performance with increasing Indigenous American (IA) ancestry, while Asian PRSs had increased performance with increasing IA ancestry. The addition of two H/L SNPs increased performance for all PRSs, most notably in the samples with high IA ancestry, and did not impact the performance of PRSs in individuals with lower IA ancestry.

A single PRS that incorporates risk variants relevant to the multiple ancestral components of individuals from Latin America, instead of a set of ancestry-specific panels, could be used in clinical practice.

The results highlight the importance of population-specific discovery and suggest a straightforward approach to integrate ancestry-specific variants into PRSs for clinical application.

The burgeoning crises of antimicrobial resistance and plastic pollution are converging in healthcare settings, presenting a complex challenge to global health. This study investigates the microbial populations in healthcare waste to understand the extent of antimicrobial resistance and the potential for plastic degradation by bacteria. Our metagenomic analysis, using both amplicon and shallow shotgun sequencing, provided a comprehensive view of the taxonomic diversity and functional capacity of the microbial consortia. The viable bacteria in healthcare waste samples were analyzed employing full-length 16S rRNA sequencing, revealing a diverse bacterial community dominated by Firmicutes and Proteobacteria phyla. Notably, Proteus mirabilis VFC3/3 and Pseudomonas sp. VFA2/3 were detected, while Stenotrophomonas maltophilia VFV3/2 surfaced as the predominant species, holding implications for the spread of hospital-acquired infections and antimicrobial resistance. Antibiotic susceptibility testing identified multidrug-resistant strains conferring antimicrobial genes, including the broad-spectrum antibiotic carbapenem, underscoring the critical need for improved waste management and infection control measures. Remarkably, we found genes linked to the breakdown of plastic that encoded for enzymes of the esterase, depolymerase, and oxidoreductase classes. This suggests that specific bacteria found in medical waste may be able to reduce the amount of plastic pollution that comes from biological and medical waste. The information is helpful in formulating strategies to counter the combined problems of environmental pollution and antibiotic resistance. This study emphasises the importance of monitoring microbial communities in hospital waste in order to influence waste management procedures and public health policy. The findings highlight the need for a multidisciplinary approach to mitigate the risks associated with antimicrobial resistance and plastic waste, especially in hospital settings where they intersect most acutely.

Treatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and gemcitabine (PG) has been shown to be superior to PF in the treatment of R/M nasopharyngeal carcinoma patients. Therefore, we hypothesise that the combination of pembrolizumab with PG would be comparable to pembrolizumab with PF as a first-line treatment in R/M HNSCC.

This is an open-label, multicentre, single-arm, phase 2 study of pembrolizumab plus PG for first-line treatment in subjects with R/M HNSCC in Malaysia. The study is conducted using the Optional Simon optimal 2-stage design. At the initial stage, 26 subjects will be enrolled and if seven or more patients achieve an objective response rate (ORR), then 63 patients will be enrolled. Subjects will be given pembrolizumab 200 mg3every 3 weeks up to 35 cycles in combination with chemotherapy for up to six cycles of platinum (either cisplatin at 35 mg/m2intravenous on day 1 and day 8 or carboplatin at area under the curve 5 intravenous on day 1 of each 3-week cycle) and gemcitabine at 1250 mg/m2intravenous on days 1 and 8 of a 3-week cycle. The primary end point is the ORR as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points include the overall survival, progression free survival, response duration and safety. The exploratory objectives include relationships of microbiome profiles, prognostic and predictive biomarkers with the clinical responses.

The study was approved by the ethics committee of the University Malaya Medical Centre (202213–10884). Findings will be disseminated through conference presentations and peer review publications.

ClinicalTrials.gov (www.clinicaltrial.gov);NCT05286619.