抗癌药物治疗仍然是治疗癌症的基石。由于遗传因素影响药物反应和代谢，抗癌药物的有效性和安全性在个体之间存在显着差异。关于斯里兰卡人与抗癌治疗相关的药物基因组变异的数据很少。由于斯里兰卡目前的治疗指南通常不考虑当地的药物基因组变异，本研究旨在探索斯里兰卡人群药物基因组变异的多样性，为个性化治疗方法和改善患者结果铺平道路。有关变异药物对的药物基因组数据从药物基因组学知识库数据库中获得了基因 CYP2D6、DPYD、NUDT15、EPAS1 和 XRCC1 的基因组，以及标记为证据级别 1A-2B 的临床注释。它们在斯里兰卡人中的频率是从匿名数据库中获得的，该数据库来自 541 名在科伦坡大学医学院人类遗传学部门接受外显子组测序的斯里兰卡人。 DPYD、NUDT15 和 EPAS1 基因的变异分别与氟嘧啶、巯基嘌呤和索拉非尼的毒性增加有关。 CYP2D6 和 XRCC1 基因的变异分别与他莫昔芬和铂化合物的功效变化有关。计算这些变异的次要等位基因频率并与其他群体进行比较。rs1065852 c.100 C > T (CYP2D6)、rs3918290 c.1905  1G > A (DPYD)、rs56038477 c.1236G > A (DPYD)的MAF， rs7557402 c .1035-7 C > G (EPAS1)、rs116855232 c.415 C > T (NUDT15*3) 和 rs25487 c.1196 A > G (XRCC1) 为：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] 和 64.0% [95%CI：61.1-66.8]，分别。斯里兰卡人中 rs1065852 c.100 C > T (CYP2D6)、rs7557402 c.1035-7 C > G (EPAS1) 和 rs25487 (XRCC1) 的频率显着较低，而 rs116855232 c.415 C > T (NUDT) 的频率显着较低15 *3) 和 rs56038477 c.1236G > A (DPYD) 在斯里兰卡人中显着高于一些西方和亚洲人群。斯里兰卡人可能会表现出较低的索拉非尼毒性风险 (rs7557402 c.84,131 C > G)，并且，氟嘧啶 (rs56038477 c.1236G > A) 和巯嘌呤 (rs116855232 c.415 C > T) 的毒性风险较高，而他莫昔芬 (rs1065852 c.100 C > T) 和铂化合物 (rs25487) 的有效性较低。这些发现强调了这些遗传变异对斯里兰卡人抗癌剂量需求个体差异的潜在贡献。© 2024。作者。

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.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.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.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.© 2024. The Author(s).