Caspase 8、9 基因多态性对非霍奇金淋巴瘤易感性及临床/病理特征的影响。
The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features.
机构信息
Department of Clinical Biochemistry, Zahedan University of Medical Sciences, Zahedan, Iran.
Children and Adolescent Health Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.
出版信息
Asian Pac J Cancer Prev. 2022 Dec 1;23(12):4339-4346. doi: 10.31557/APJCP.2022.23.12.4339.
BACKGROUND
Caspases (CASPs) are the main executors of the apoptotic process. Studies to date have shown the role of caspase-8 (CASP8) and caspase-9 (CASP9) in carcinogenesis. Therefore, the aim of this study was to investigate the associations between CASP9-rs4233532, CASP9-rs4646018, and CASP8- rs1045485 gene polymorphisms and non-Hodgkin lymphoma (NHL) susceptibility in an Iranian population-based study. Moreover, it was examined whether such the genotype of these polymorphisms is related with clinicopathological characteristics of NHL.
METHODS
175 patients with NHL and 175 age- and sex-matched controls were enrolled in this study. We determined the genotypes of single nucleotide polymorphisms (SNPs) from CASP genes with Tetra ARMS-PCR (Amplification refractory mutation system) method.
RESULTS
Statistically significant association were observed between CASP9-rs4646018 and increased risk of NHL under codominant CC, codominant TC, and dominant TC+CC genetic models. Our results showed that the A allele of CASP8-rs1045485 was a protective factor for NHL and GArs1045485 genotype significantly reduced risk of NHL. In contrast, CASP9- rs4233532 was not linked to NHL susceptibility. No relationship was detected between CASP8-rs1045485 and CASP9-rs4233532 and NHL clinicopathological characteristics, however genetic variation in CASP9-rs4646018 was associated with histology, treatment and radio therapy of NHL.
CONCLUSIONS
Our study presented that the CASP8- rs1045485 and CASP9-rs4646018 polymorphisms could affect the risk of NHL in Iranian populations which was the first report to show the significant relationship between rs1045485, rs4646018 polymorphisms and NHL susceptibility. Replication large-scale case-control studies in different ethnicities are warranted to verify these findings.
背景
Caspases(CASPs)是细胞凋亡过程的主要执行者。迄今为止的研究表明,caspase-8(CASP8)和 caspase-9(CASP9)在肿瘤发生中起作用。因此,本研究旨在探讨伊朗人群中 CASP9-rs4233532、CASP9-rs4646018 和 CASP8-rs1045485 基因多态性与非霍奇金淋巴瘤(NHL)易感性之间的关系。此外,还研究了这些多态性的基因型是否与 NHL 的临床病理特征有关。
方法
本研究纳入了 175 例 NHL 患者和 175 名年龄和性别匹配的对照。我们采用 Tetra ARMS-PCR(扩增受阻突变系统)法检测 CASP 基因单核苷酸多态性(SNP)的基因型。
结果
在共显性 CC、共显性 TC 和显性 TC+CC 遗传模型下,CASP9-rs4646018 与 NHL 发病风险增加存在统计学显著相关性。我们的结果表明,CASP8-rs1045485 的 A 等位基因是 NHL 的保护因素,GArs1045485 基因型显著降低 NHL 的发病风险。相反,CASP9-rs4233532 与 NHL 易感性无关。CASP8-rs1045485 和 CASP9-rs4233532 与 NHL 临床病理特征之间未发现相关性,然而,CASP9-rs4646018 的遗传变异与 NHL 的组织学、治疗和放疗有关。
结论
本研究表明,CASP8-rs1045485 和 CASP9-rs4646018 多态性可能影响伊朗人群 NHL 的发病风险,这是首次报道 rs1045485、rs4646018 多态性与 NHL 易感性之间存在显著关系。需要在不同种族中进行更大规模的病例对照研究来验证这些发现。