Excision Repair Cross-Complementation Group 1 (ERCC1) Polymorphism Predicted Platinum-Based Chemotherapy Treatment Outcome in Cholangiocarcinoma

Thanachai Sanlung¹, Prakasit Sa-Ngiamwibul², Aumkhae Sookprasert¹, Jarin Chindaprasirt¹, Attapol Titapun³, Sarinya Kongpetch⁴, Areerat Dornsena⁴, Thikhumporn Areesinpitak⁴, Wichittra Tassaneeyakul⁴, Suda Vannaprasaht⁴, Kosin Wirasorn¹

Affiliation : ¹ Medical Oncology Unit, Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand ² Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand ³ Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand ⁴ Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

Background: Platinum-based chemotherapy is an effective cytotoxic treatment for many cancers. ERCC1 and ERCC2 are major enzymes involved in nucleotide excision repair (NER), influencing mRNA level and stability. ERCC1 polymorphism has been identified as a predictive biomarker for platinum treatment in several cancers. The prevalence of ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs1799793, and ERCC2 rs13181 are statistically significant in Japanese and Caucasian populations. However, data on Cholangiocarcinoma (CCA) are limited.
Objective: To investigate an associational study in ERCC1 and ERCC2 polymorphism and the clinical outcome of platinum-based therapy in cholangiocarcinoma.
Materials and Methods: The authors conducted a retrospective review of clinical data and analyzed genomic DNA from formalin-fixed paraffinembedded tissue obtained from patients diagnosed with locally advanced or metastatic CCA who underwent palliative chemotherapy.
Results: Among 54 patients, those with the ERCC1 rs11615 heterozygous SNP (CT) exhibited a trend toward better overall survival compared to the wild type (CC), with 8.8 months versus 6.3 months, respectively. The hazard ratio (HR) was statistically significant in multivariate survival analysis (HR 0.47, 95% CI 0.23 to 0.94, p=0.032). These findings were also associated with improved objective response and disease control rates. No significant association was found between efficacy and ERCC1 rs3212986 (C>A), ERCC2 rs1799793 (C>T), or ERCC2 rs13181 (A>C) mutations.
Conclusion: The ERCC1 rs11615 heterozygous mutant showed prolonged survival, better response, and disease control rates.

Received 1 April 2024 | Revised 30 April 2024 | Accepted 9 May 2024
DOI: 10.35755/jmedassocthai.2024.S01.S63-S70

Keywords : Cholangiocarcinoma; ERCC1; Polymorphism; Platinum-base; Survival; Response

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