Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kelantan Malaysia.
Asian Pac J Cancer Prev. 2021 Feb 1;22(2):565-571. doi: 10.31557/APJCP.2021.22.2.565.
The FAS mediated apoptosis pathway involving the FAS and FASL genes plays a crucial role in the regulation of apoptotic cell death and imatinib mesylate (IM) mechanism of action. Promoter polymorphisms FAS-670 A>G and FAS-844 T>C which alter the transcriptional activity of these genes may grant a risk to develop cancer and revamp the drug activities towards the cancer cell. We investigated the association of these two polymorphisms with the susceptibility risk and IM treatment response in Malaysian chronic myeloid leukaemia (CML) patients.
This is a retrospective study, which included 93 CML patients and 98 controls. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the FAS and FASL polymorphisms. Data nanlysis was done using SPSS Version 22. The associations of the genotypes with susceptibility risk and IM response in CML patients were assessed by means of logistic regression analysis and deriving odds ratio with 95% CI.
We observed a significant association between FASL-844T>C polymorphism and CML susceptibility risk and IM response. Variant C allele and FASL-844 CC variant genotype carriers had significantly higher risk for CML susceptibility (OR 1.756, CI 1.163-2.652, p=0.007 and OR 2.261, CI 1.013-5.047, p=0.047 respectively). Conversely, the heterozygous genotype FASL-844 TC conferred lower risk for CML susceptibility (OR 0.379, CI 0.176-0.816, p=0.013). The heterozygous and homozygous variant genotypes and variant C alleles were found to confer a lower risk for the development of IM resistance with OR 0.129 (95% CI: 0.034-0.489 p=0.003), OR 0.257 (95% CI: 0.081-0.818, p=0.021), and OR 0.486 (95% CI: 0.262-0.899, p=0.021) respectively. We also found that FAS-670 A>G polymorphism was not associated with CML susceptibility risk or IM response.
The genetic polymorphism FASL-844 T>C may contribute to the CML susceptibility risk and also IM treatment response in CML patients. Accodringly, it may be useful as a biomarker for predicting CML susceptibility risk and IM resistance.
FAS 介导的细胞凋亡途径涉及 FAS 和 FASL 基因，在调节细胞凋亡和伊马替尼甲磺酸盐（IM）作用机制方面起着至关重要的作用。启动子多态性 FAS-670A>G 和 FAS-844T>C 改变这些基因的转录活性，可能会增加患癌症的风险，并改变药物对癌细胞的作用。我们研究了这两种多态性与马来西亚慢性髓性白血病（CML）患者的易感性风险和 IM 治疗反应之间的关系。
这是一项回顾性研究，包括 93 例 CML 患者和 98 例对照。采用聚合酶链反应限制性片段长度多态性（PCR-RFLP）方法对 FAS 和 FASL 多态性进行基因分型。数据分析采用 SPSS 版本 22。通过逻辑回归分析和推导 95%置信区间的比值比，评估基因型与 CML 患者易感性风险和 IM 反应的关系。
我们观察到 FASL-844T>C 多态性与 CML 易感性风险和 IM 反应之间存在显著相关性。变体 C 等位基因和 FASL-844CC 变体基因型携带者患 CML 的风险显著增加（OR 1.756，CI 1.163-2.652，p=0.007 和 OR 2.261，CI 1.013-5.047，p=0.047）。相反，杂合基因型 FASL-844TC 患 CML 的风险较低（OR 0.379，CI 0.176-0.816，p=0.013）。杂合和纯合变体基因型和变体 C 等位基因被发现可降低 IM 耐药的风险，OR 0.129（95%CI：0.034-0.489，p=0.003），OR 0.257（95%CI：0.081-0.818，p=0.021）和 OR 0.486（95%CI：0.262-0.899，p=0.021）。我们还发现 FAS-670A>G 多态性与 CML 易感性风险或 IM 反应无关。
FASL-844T>C 遗传多态性可能导致 CML 易感性风险和 CML 患者的 IM 治疗反应。因此，它可能作为预测 CML 易感性风险和 IM 耐药的生物标志物有用。
