Background: Therapy with anti-cancer drugs remain the cornerstone of treating cancer. The effectiveness and safety of anti-cancer drugs vary significantly among individuals due to genetic factors influencing the drug response and metabolism. Data on the pharmacogenomic variations in Sri Lankans related to anti-cancer therapy is sparse. As current treatment guidelines in Sri Lanka often do not consider local pharmacogenomic variants, this study aimed to explore the diversity of pharmacogenomic variants in the Sri Lankan population to pave the way for personalized treatment approaches and improve patient outcomes.
Methods: Pharmacogenomic data regarding variant-drug pairs of genes CYP2D6, DPYD, NUDT15, EPAS1, and XRCC1 with clinical annotations labelled as evidence levels 1A-2B were obtained from the Pharmacogenomics Knowledgebase database. Their frequencies in Sri Lankans were obtained from an anonymized database that was derived from 541 Sri Lankans who underwent exome sequencing at the Human Genetics Unit, Faculty of Medicine, University of Colombo. Variations in DPYD, NUDT15, and EPAS1 genes are related to increased toxicity to fluoropyrimidines, mercaptopurines, and sorafenib respectively. Variations in CYP2D6 and XRCC1 genes are related to changes in efficacy of tamoxifen and platinum compounds, respectively. Minor allele frequencies of these variants were calculated and compared with other populations.
Results: MAFs of rs1065852 c.100 C > T (CYP2D6), rs3918290 c.1905 + 1G > A (DPYD), rs56038477 c.1236G > A (DPYD), rs7557402 c.1035-7 C > G (EPAS1), rs116855232 c.415 C > T (NUDT15*3), and rs25487 c.1196 A > G (XRCC1) were: 12.9% [95%CI:10.9-14.9], 1.5% [95%CI:0.8-2.2], 1.2% [95%CI:0.5-1.8], 37.7% [95%CI:34.8-40.6], 8.3% [95%CI:6.7-10.0], and 64.0% [95%CI:61.1-66.8], respectively. Frequencies of rs1065852 c.100 C > T (CYP2D6), rs7557402 c.1035-7 C > G (EPAS1), and rs25487 (XRCC1) were significantly lower in Sri Lankans, while frequencies of rs116855232 c.415 C > T (NUDT15*3) and rs56038477 c.1236G > A (DPYD) were significantly higher in Sri Lankans when compared to some Western and Asian populations.
Conclusion: Sri Lankans are likely to show lower toxicity risk with sorafenib (rs7557402 c.84,131 C > G) and, higher toxicity risk with fluoropyrimidines (rs56038477 c.1236G > A) and mercaptopurine (rs116855232 c.415 C > T), and reduced effectiveness with tamoxifen (rs1065852 c.100 C > T) and platinum compounds (rs25487). These findings highlight the potential contribution of these genetic variations to the individual variability in anti-cancer dosage requirements among Sri Lankans.
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http://dx.doi.org/10.1186/s12920-024-01919-2 | DOI Listing |
J Med Case Rep
December 2024
Department of Pathology, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka.
Introduction: Primary bone marrow diffuse large B-cell lymphoma is a rare clinical entity, and the "bone marrow-liver-spleen" type of diffuse large B-cell lymphoma is rarer, with only a few published cases in literature. Though bone marrow-liver-spleen-type diffuse large B-cell lymphoma has unique presentations such as fever, cytopenias, and hemophagocytic lymphohistiocytosis, no cases with cold autoimmune hemolytic anemia have been reported.
Case Presentation: A 39-year-old Sri Lankan woman, previously healthy, presented with shortness of breath, productive cough, and fever for 4 days.
Cureus
November 2024
University Medical Unit, Batticaloa Teaching Hospital, Batticaloa, LKA.
Background: Deliberate self-harm (DSH) by poisoning is a significant public health concern worldwide. This study aimed to analyze the demographic, socioeconomic, and psychological factors contributing to self-harm by poisoning in patients admitted to a tertiary care hospital in Sri Lanka.
Methods: A cross-sectional study was conducted on 101 patients admitted to the hospital for poisoning-related self-harm.
BMC Public Health
December 2024
Consultant Community Physician, Health Promotion Bureau, Ministry of Health, Nutrition and Indigenous Medicine, Colombo, Sri Lanka.
Background: An unhealthy diet is a key risk factor for non-communicable diseases (NCD), which account for a significant number of premature deaths and disability-adjusted life years worldwide. Office workers are reported to have unhealthy and unbalanced diets, while being sedentary due to the nature of their work, placing them at a greater risk of NCD. This study aimed to determine dietary intake and associated factors among sedentary office workers in Southern Sri Lanka.
View Article and Find Full Text PDFJ Infect Dev Ctries
November 2024
Department of Pharmacology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka.
Pest Manag Sci
December 2024
Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insects, Zhejiang Key Laboratory of Biology and Ecological Regulation of Crop Pathogens and Insects, Institute of Insect Sciences, Zhejiang University, Hangzhou, China.
Background: Vector-borne viruses often manipulate plant defenses against insect vectors, thereby impacting vector population dynamics and in turn virus spread. However, the factors regulating the outcome of insect vector-virus-plant tripartite interactions, such as the feature of virus-vector combinations, are understudied.
Results: Using eight whitefly (Bemisia tabaci)-begomovirus combinations exhibiting different degrees of competence, namely virus transmission efficiency, we examined the association between whitefly-begomovirus competence and plant-mediated mutualism.
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