UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy: a retrospective study

BMC Cancer. 2020 Aug 5;20(1):729. doi: 10.1186/s12885-020-07225-1.

Abstract

Background: Uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) is a predictive biomarker for the side-effects of irinotecan chemotherapy, which reduces the volume of tumors harboring UGT1A1 polymorphisms. We aimed to determine whether UGT1A1 polymorphisms can predict progression-free survival in patients with local cervical cancer treated with irinotecan chemotherapy.

Methods: We retrospectively analyzed the data of 51 patients with cervical cancer treated at a single institution between 2010 and 2015. All patients were diagnosed with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IB1, IB2, IIA, or IIB squamous cell carcinoma, underwent radical hysterectomy, and received irinotecan chemotherapy as neoadjuvant and/or adjuvant treatment. All patients were examined for irinotecan side effects using UGT1A1 tests. Conditional inference tree and survival analyses were performed considering the FIGO stage, age, the UGT1A1 status, and the number of metastatic lymph nodes to determine primary factors associated with progression-free survival.

Results: The tree-structured survival model determined high recurrence-risk factors related to progression-free survival. The most relevant factor was ≥2 metastatic lymph nodes (p = 0.004). The second most relevant factor was UGT1A1 genotype (p = 0.024). Among patients with ≤1 metastatic lymph node, those with UGT1A1 polymorphisms benefited from irinotecan chemotherapy and demonstrated significantly longer progression-free survival (p = 0.020) than those with wild-type UGT1A1.

Conclusions: Irinotecan chemotherapy might be beneficial in patients with cervical cancer, UGT1A1 polymorphisms, and ≤ 1 metastatic lymph nodes.

Keywords: Irinotecan chemotherapy; UGT1A1 polymorphisms; Uterine cervical cancer.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Chemotherapy, Adjuvant
  • Female
  • Glucuronosyltransferase / genetics*
  • Humans
  • Hysterectomy
  • Irinotecan / adverse effects
  • Irinotecan / therapeutic use*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Organoplatinum Compounds / therapeutic use
  • Pelvis
  • Polymorphism, Genetic*
  • Prognosis
  • Progression-Free Survival
  • Retrospective Studies
  • Survival Analysis
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Irinotecan
  • nedaplatin
  • UGT1A1 enzyme
  • Glucuronosyltransferase