Cancers (Basel). 2021;13(6):cancers13061196.

Excision Repair Cross-Complementation Group 6 Gene Polymorphism Is Associated with the Response to FOLFIRINOX Chemotherapy in Asian Patients with Pancreatic Cancer.

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제1저자 최영훈, 임영균 · 교신저자 류지곤

PMID 33801891 PMC7998301 DOI 10.3390/cancers13061196 IF 4.8 소화기내과

소속 (3)

Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea.
Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 03080, Korea.

Abstract

FOLFIRINOX is currently one of the standard chemotherapy regimens for pancreatic cancer patients, but little is known about the factors that can predict a response to it. We performed a study to discover novel DNA damage repair (DDR) gene variants associated with the response to FOLFIRINOX chemotherapy in patients with pancreatic cancer. We queried a cohort of pancreatic cancer patients who received FOLFIRINOX chemotherapy as the first treatment and who had tissue obtained through an endoscopic ultrasound-guided biopsy that was suitable for DNA sequencing. We explored variants of 148 DDR genes based on whole exome sequencing and performed multivariate Cox regression to find genetic variants associated with progression-free survival (PFS). Overall, 103 patients were included. Among 2384 variants of 141 DDR genes, 612 non-synonymous variants of 123 genes were selected for Cox regression analysis. The multivariate Cox model showed that rs2228528 in ERCC6 was significantly associated with improved PFS (hazard ratio 0.54, p = 0.001). The median PFS was significantly longer in patients with rs2228528 genotype AA vs. genotype GA and GG (23.5 vs. 16.2 and 8.6 months; log-rank p < 0.001). This study suggests that rs2228528 in ERCC6 could be a potential predictor of response to FOLFIRINOX chemotherapy in patients with pancreatic cancer.

Keywords

DNA repairERCC6FOLFIRINOXpancreatic cancerprogression-free survival

Figures

**Figure 1** Flow chart of patient enrollment. The flowchart shows the patient exclusion criteria and the final number of patients included in the study.

**Figure 2** Schematic diagram of genetic variant analysis. The schematic diagram shows how genetic variants were selected and analyzed from whole exome sequencing data. Abbreviation: WXS, whole exome sequencing.

**Figure 3** Progression-free survival according to genotype of rs2228528 in ERCC6. Patients were divided according to rs2228528 genotypes: AA (n = 23), GA (n = 41), and GG (n = 39), and assessed for progression-free survival using the Kaplan–Meier method and the log-rank test.

그림 출처: PubMed Central 공개 논문 (PMC7998301)

Conflict of interest statement

The authors declare no conflict of interest.

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