- Gastrointestinal Cancer
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Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer
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Si-Qi Dong, Tong-Min Wang, Jiang-Bo Zhang, Yong-Qiao He, Wen-Qiong Xue, Zi-Yi Wu, Da-Wei Yang, Lian-Jing Cao, Jing-Wen Huang, Xi-Zhao Li, Pei-Fen Zhang, Xiao-Hui Zheng, Wei-Hua Jia
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Cancer Res Treat. 2021;53(3):724-732. Published online December 2, 2020
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DOI: https://doi.org/10.4143/crt.2020.457
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 Abstract
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- Purpose
Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients.
Materials and Methods
Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model.
Results
We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression.
Conclusion
This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.
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Citations
Citations to this article as recorded by  - The Association Between Thymidylate Synthase Gene Polymorphisms and the Risk of Ischemic Stroke in Chinese Han Population
Fuhua Yu, Lei Shi, Qianru Wang, Xiaohui Xing, Zhongchen Li, Lei Hou, Zhengshan Zhou, Zengguang Wang, Yilei Xiao
Biochemical Genetics.2024; 62(1): 468. CrossRef - MTHFR 677 C>T- and 1298 A>C-related adverse effects in 5-fluorouracil-based chemotherapy in the Asian population: a systematic review and meta-analysis
Yu Bai, Dan Jiang, Yong-qing Wen, Wen-juan Wang, Zai-wei Song
Discover Medicine.2024;[Epub] CrossRef - Influence of Single-Nucleotide Polymorphisms on Clinical Outcomes of Capecitabine-Based Chemotherapy in Colorectal Cancer Patients: A Systematic Review
Yasmin Cura, Cristina Pérez-Ramírez, Almudena Sánchez-Martín, Cristina Membrive-Jimenez, María Isabel Valverde-Merino, Encarnación González-Flores, Alberto Jiménez Morales
Cancers.2023; 15(6): 1821. CrossRef - Capecitabine
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Frontiers in Endocrinology.2022;[Epub] CrossRef - DPYD Exome, mRNA Expression and Uracil Levels in Early Severe Toxicity to Fluoropyrimidines: An Extreme Phenotype Approach
Priscila Villalvazo, Belén Marzal-Alfaro, Pilar García-Alfonso, José Luis Revuelta-Herrero, Fabienne Thomas, Sara López-Tarruella, Xandra García-González, Aitana Calvo, Malika Yakoubi, Sara Salvador-Martín, Flora López-López, Iker Aguilar, María Sanjurjo-
Journal of Personalized Medicine.2021; 11(8): 792. CrossRef
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