2nd Propaedeutic Department of Internal Medicine, National & Kapodistrian University of Athens, ATTIKON University Hospital, 12462 Athens, Greece.
Hellenic Genito-Urinary Cancer Group, 89 Evrou St, 11527 Athens, Greece.
Curr Oncol. 2021 Nov 5;28(6):4474-4484. doi: 10.3390/curroncol28060380.
We previously showed that ERCC1 19007 C>T polymorphism was associated with cancer-specific survival (CSS) after platinum-based chemotherapy in patients with advanced urothelial cancer (aUC). We aimed to confirm this association in a different cohort of patients. Genotyping of the 19007C>T polymorphism was carried out by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP) in 98 aUC patients, treated with platinum-based chemotherapy. Median age of the patients was 68.8, 13.3% of them were female, 90.8% had ECOG PS of 0 or 1, and 48% received cisplatin-based chemotherapy. In addition to chemotherapy, 32.7% of the patients received immunotherapy, and 19.4% vinflunine. Eighty-one patients (82.7%) were carriers of the 19007T polymorphic allele: 46 (46.9%) were heterozygotes, and 35 (35.7%) were homozygotes. The ERCC1 polymorphism was not associated with CSS, progression-free (PFS), or overall (OS) survival in the total population. Nevertheless, there was a significant interaction between the prognostic significance of ERCC1 polymorphism and the use of modern immunotherapy: the T allele was associated with worse outcome in patients who received chemotherapy only, while this association was lost in patients who received both chemotherapy and immune checkpoint inhibitors. Our study suggests that novel therapies may influence the significance of ERCC1 polymorphism in patients with aUC. Its determination may be useful in the changing treatment landscape of the disease.
我们之前的研究表明，ERCC1 19007C>T 多态性与晚期尿路上皮癌（aUC）患者接受铂类化疗后的癌症特异性生存（CSS）相关。我们旨在通过对 98 名接受铂类化疗的 aUC 患者的聚合酶链反应（PCR）扩增和限制性片段长度多态性（RFLP）来确认这一多态性在不同患者队列中的相关性。患者的中位年龄为 68.8 岁，13.3%为女性，90.8%的患者体能状态（ECOG PS）为 0 或 1，48%的患者接受了顺铂类化疗。除化疗外，32.7%的患者接受了免疫治疗，19.4%的患者接受了 vinflunine。81 名患者（82.7%）为 19007T 多态性等位基因的携带者：46 名（46.9%）为杂合子，35 名（35.7%）为纯合子。该 ERCC1 多态性与 CSS、无进展生存期（PFS）或总生存期（OS）在总体人群中均无相关性。然而，ERCC1 多态性的预后意义与现代免疫治疗的使用之间存在显著的交互作用：在仅接受化疗的患者中，T 等位基因与较差的预后相关，而在同时接受化疗和免疫检查点抑制剂的患者中，这种相关性消失了。我们的研究表明，新的治疗方法可能会影响 aUC 患者 ERCC1 多态性的意义。在疾病治疗格局不断变化的情况下，其测定可能是有用的。
