Laboratório de Mutagênese e Oncogenética, Departamento de Biologia Geral, Universidade Estadual de Londrina, Paraná, Brazil.
Hospital do Câncer de Londrina, Paraná, Brazil.
Anticancer Res. 2023 Jan;43(1):369-379. doi: 10.21873/anticanres.16172.
BACKGROUND/AIM: Prostate cancer (PCa) is one of the most frequent neoplasms in men around the world. In recent years, the search for new biomarkers with greater prognostic potential for PCa has intensified. This study aimed to evaluate single nucleotide polymorphisms (SNPs) and a combined panel of these polymorphisms in relation to biochemical recurrence in patients who were through prostatectomy, with an average of 7 years of follow-up.
Patients diagnosed with PCa (n=197) participated in this cohort study. Thirteen SNPs were analyzed: rs2279115 (BCL-2), rs26677604 (CASP3), rs1052571 (CASP9), rs11781886 (NKX3-1), rs2735343 (PTEN), rs2494750 (AKT1), rs2699887 (PI3KCA), rs3195676 (AMACR), rs17302090 (AR), rs2536 (mTOR), rs1695 (GSTP1), rs2308321 (MGMT) and rs1544410 (VDR). Variants were combined and four main panels were defined: cell death, cell survival, growth receptors, and metabolism. Genotyping was performed by real-time PCR.
We did not observe any significant relation between the panels of variants analyzed, apart from the rare allele (G) of rs2308321 (MGMT) that was associated with a higher risk of recurrence (p=0.036) when compared to the prevalent (A) in the allelic model.
This MGMT variant occurs in an exon, and it could potentially affect DNA repair and, therefore, the biochemical relapse of PCa patients.
背景/目的:前列腺癌(PCa)是全球男性中最常见的肿瘤之一。近年来,人们强烈地希望找到具有更大预后潜力的新生物标志物来诊断 PCa。本研究旨在评估单核苷酸多态性(SNPs)以及这些多态性的联合组合与前列腺切除术患者生化复发的关系,这些患者的平均随访时间为 7 年。
本队列研究纳入了 197 例诊断为 PCa 的患者。分析了 13 个 SNPs:rs2279115(BCL-2)、rs26677604(CASP3)、rs1052571(CASP9)、rs11781886(NKX3-1)、rs2735343(PTEN)、rs2494750(AKT1)、rs2699887(PI3KCA)、rs3195676(AMACR)、rs17302090(AR)、rs2536(mTOR)、rs1695(GSTP1)、rs2308321(MGMT)和 rs1544410(VDR)。对变体进行组合并定义了四个主要的组合:细胞死亡、细胞存活、生长受体和代谢。通过实时 PCR 进行基因分型。
除了在等位基因模型中,与常见(A)相比,rs2308321(MGMT)的罕见等位基因(G)与更高的复发风险相关(p=0.036)之外,我们没有观察到分析的变体组合之间存在任何显著关系。
该 MGMT 变体发生在一个外显子中,可能会影响 DNA 修复,从而影响 PCa 患者的生化复发。