The Role of Single-Nucleotide Polymorphisms in Cholangiocarcinoma: A Systematic Review

Guanwu Wang, Lara Rosaline Heij, Dong Liu, Edgar Dahl, Sven Arke LANG, Tom Florian Ulmer, Tom LUEDDE, Ulf Peter Neumann, Jan Bednarsch*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

5 Citations (Scopus)
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Single-nucleotide polymorphisms (SNPs) play an essential role in various malignancies, but their role in cholangiocarcinoma (CCA) remains to be elucidated. Therefore, the purpose of this systematic review was to evaluate the association between SNPs and CCA, focusing on tumorigenesis and prognosis. A systematic literature search was carried out using PubMed, Embase, Web of Science and the Cochrane database for the association between SNPs and CCA, including literature published between January 2000 and April 2022. This systematic review compiles 43 SNPs in 32 genes associated with CCA risk, metastatic progression and overall prognosis based on 34 studies. Susceptibility to CCA was associated with SNPs in genes related to inflammation (PTGS2/COX2, IL6, IFNG/IFN-γ, TNF/TNF-α), DNA repair (ERCC1, MTHFR, MUTYH, XRCC1, OGG1), detoxification (NAT1, NAT2 and ABCC2), enzymes (SERPINA1, GSTO1, APOBEC3A, APOBEC3B), RNA (HOTAIR) and membrane-based proteins (EGFR, GAB1, KLRK1/NKG2D). Overall oncological prognosis was also related to SNPs in eight genes (GNB3, NFE2L2/NRF2, GALNT14, EGFR, XRCC1, EZH2, GNAS, CXCR1). Our findings indicate that multiple SNPs play different roles at various stages of CCA and might serve as biomarkers guiding treatment and allowing oncological risk assessment. Considering the differences in SNP detection methods, patient ethnicity and corresponding environmental factors, more large-scale multicentric investigations are needed to fully determine the potential of SNP analysis for CCA susceptibility prediction and prognostication.

Original languageEnglish
Article number5969
Issue number23
Publication statusPublished - 2 Dec 2022

Bibliographical note

Funding Information:
Guanwu Wang was funded by the China Scholarship Council (Grant number: 202108430018). Dong Liu was funded by the China Scholarship Council (Grant number: 202208080011). This project was supported by the German Research Foundation (SFB-CRC 1382-A01).

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© 2022 by the authors.


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