Soares Sílvia, Nogueira Augusto, Coelho Ana, Assis Joana, Pereira Deolinda, Bravo Isabel, Medeiros Rui
1 Molecular Oncology and Viral Pathology Group - Research Center, Portuguese Institute of Oncology, Porto - Portugal.
3 Research Department, Portuguese League Against Cancer (NRNorte), Porto - Portugal.
Int J Biol Markers. 2018 Jan;33(1):116-123. doi: 10.5301/ijbm.5000279.
Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be considered potential biomarkers in the prognosis and therapeutic response of cancer patients. The present study investigated the association between ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms and clinical toxicities induced by chemoradiotherapy (CRT) in cervical cancer.
This hospital-based retrospective cohort study included 260 patients with cervical cancer, FIGO stages Ib2-IVa, who underwent CRT (cisplatin). Genetic polymorphisms analysis was performed by allelic discrimination with real-time polymerase chain reaction (RT-PCR).
Our results indicated a link between ERCC1 rs3212986 and the onset of late gastrointestinal toxicity (p = 0.038). Furthermore, using a recessive model (AA vs. CC/CA), we found that patients carrying AA homozygous genotype presented a fourfold increased risk of developing late gastrointestinal toxicity when compared with patients with the C allele (odds ratio = 3.727, 95% confidence interval, 1.199-11.588; p = 0.017). No association was found regarding the XRCC3 rs861539 polymorphism and any clinical toxicity event.
This is the first study evaluating the relationship between these polymorphisms and clinical toxicities in cervical cancer patients submitted to CRT with cisplatin. These results may contribute toward a better understanding of the influence of genetic polymorphisms in genes associated with DNA repair in the clinical response to CRT of patients with cervical cancer.
多项研究表明,存在一些单核苷酸多态性(SNP)可被视为癌症患者预后和治疗反应的潜在生物标志物。本研究调查了ERCC1 rs3212986和XRCC3 rs861539多态性与宫颈癌放化疗(CRT)诱导的临床毒性之间的关联。
这项基于医院的回顾性队列研究纳入了260例FIGO分期为Ib2-IVa期的宫颈癌患者,这些患者接受了CRT(顺铂)治疗。通过实时聚合酶链反应(RT-PCR)进行等位基因鉴别来进行基因多态性分析。
我们的结果表明ERCC1 rs3212986与晚期胃肠道毒性的发生之间存在关联(p = 0.038)。此外,使用隐性模型(AA与CC/CA),我们发现携带AA纯合基因型的患者发生晚期胃肠道毒性的风险比携带C等位基因的患者增加了四倍(优势比 = 3.727,95%置信区间,1.199 - 11.588;p = 0.017)。未发现XRCC3 rs861539多态性与任何临床毒性事件之间存在关联。
这是第一项评估这些多态性与接受顺铂CRT的宫颈癌患者临床毒性之间关系的研究。这些结果可能有助于更好地理解与DNA修复相关基因中的基因多态性对宫颈癌患者CRT临床反应的影响。