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XRCC1和TP53基因多态性与非小细胞肺癌诊断时的晚期疾病及早期远处转移相关。

The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

作者信息

Karaağaç Mustafa, Geredeli Çağlayan, Yıldırım Mahmut Selman, Altınok Tamer, Dede İsa, İnal Ali, Zamani Ayşe Gül, Kaya Buğra, Demirkazık Ahmet, Artaç Mehmet

机构信息

Department of Medical Oncology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey.

Department of Thoracic Surgery, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey.

出版信息

J Cancer Res Ther. 2023 Jul-Sep;19(5):1248-1254. doi: 10.4103/jcrt.jcrt_1657_21.

Abstract

BACKGROUND

Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC.

OBJECTIVE

This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC.

MATERIAL AND METHODS

In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis.

RESULTS

The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031).

CONCLUSIONS

We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

摘要

背景

非小细胞肺癌(NSCLC)单核苷酸多态性(SNP)研究表明,DNA修复能力可能对疾病复发和生存具有预后意义。然而,尚无研究调查NSCLC患者初始诊断时SNP与转移风险之间的关系。

目的

本研究旨在探讨SNP在检测NSCLC患者初始诊断时转移风险及预后不良方面的潜在预测价值。

材料与方法

在这项前瞻性队列研究中,我们评估了275例NSCLC患者。通过聚合酶链反应对外周血细胞的SNP进行分析。结合转移的发生情况,评估切除修复交叉互补组1(ERCC1)-Asn118Asn、切除修复交叉互补组2(ERCC2)-Lys751Gln、X射线修复交叉互补组1(XRCC1)-Arg399Gln和肿瘤蛋白53(TP53)-Arg72Pro多态性。

结果

ERCC1正常基因型、ERCC2杂合子基因型、XRCC1正常基因型和TP53正常基因型与初始诊断时更高分期及更晚期疾病相关(P分别为0.027、0.005、<0.001和0.006)。此外,XRCC1正常基因型和TP53正常基因型与初始诊断时的转移风险相关(P分别为<0.001和0.002)。而且,XRCC1正常基因型与初始诊断时的脑转移风险相关(P = 0.031)。

结论

我们表明,SNP与NSCLC患者初始诊断时更高分期及更晚期疾病相关,XRCC1和TP53基因多态性与转移风险相关。这些结果可能有助于识别高危人群,并可能有助于NSCLC患者的早期诊断和治疗。

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