@article{34d23abe8fda4251a9747d3068eb49ca,
title = "Genetic variants in MAPK10 modify renal cell carcinoma susceptibility and clinical outcomes",
abstract = "Aims: The mitogen-activated protein kinase (MAPK) cascades integrate various upstream signals to regulate many cellular functions, including proliferation, differentiation, and survival. Dysregulation of these pathways has been implicated in the occurrence and progression of a variety of cancers. Main methods: This study aimed to assess the association of 192 single nucleotide polymorphisms in 22 MAPK cascade genes with renal cell carcinoma (RCC) risk and survival in 312 patients and 318 controls. Key findings: After multiple testing correction and multivariate analysis, the minor T allele of MAPK10 rs12648265 remained associated with a lower risk of RCC (adjusted odds ratio 0.64, 95% confidence interval 0.50–0.82, P = 0.000426) and metastasis (adjusted hazard ratio 0.50, 95% confidence interval 0.30–0.82, P = 0.006). Presence of the rs12648265 T allele demonstrated a trend towards being associated with increased MAPK10 expression, and meta-analysis of four RCC datasets indicated that high MAPK10 expression is associated with a favourable prognosis. Furthermore, activation of MAPK10 by the potent agonist anisomycin inhibited RCC cell growth in vitro, suggesting an involvement of MAPK10 in RCC progression. Significance: In conclusion, MAPK10 may be a meaningful biomarker and a potential therapeutic target in RCC.",
keywords = "Genetic susceptibility, Mitogen-activated protein kinase, Renal cell carcinoma, Single nucleotide polymorphisms, Survival",
author = "Tsai, {Yuan Chin} and Huang, {Chao Yuan} and Hsueh, {Yu Mei} and Fan, {Yu Ching} and Fong, {Yu Cin} and Huang, {Shu Pin} and Geng, {Jiun Hung} and Chen, {Lih Chyang} and Lu, {Te Ling} and Bao, {Bo Ying}",
note = "Funding Information: This work was supported by the Ministry of Science and Technology of Taiwan (grant nos: 106-2314-B-002-235-MY3, 108-2813-C-039-148-B, 108-2314-B-037-029, 108-2314-B-037-026-MY2, and 108-2320-B-039-050-MY3), the Kaohsiung Medical University Hospital (grant nos: KMUH105-5R42, KMUH108-8R53 and KMUH108-8R55), the Kaohsiung Medical University Research Center (grant no: KMU-TC108A04-4), and the China Medical University (grant nos: CMU109-MF-65, CMU109-SR-64 and CMU108-MF-50). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. The Authors thank Chao-Shih Chen for data analysis, and Professor Shiow-Lin Pan and the National Center for Genome Medicine, Ministry of Science and Technology of Taiwan, for technical support. The results published here are based in part on data generated by the HaploReg, 1000 Genomes, HapMap, and TCGA projects. Funding Information: This work was supported by the Ministry of Science and Technology of Taiwan (grant nos: 106-2314-B-002-235-MY3 , 108-2813-C-039-148-B , 108-2314-B-037-029 , 108-2314-B-037-026-MY2 , and 108-2320-B-039-050-MY3 ), the Kaohsiung Medical University Hospital (grant nos: KMUH105-5R42 , KMUH108-8R53 and KMUH108-8R55 ), the Kaohsiung Medical University Research Center (grant no: KMU-TC108A04-4 ), and the China Medical University (grant nos: CMU109-MF-65 , CMU109-SR-64 and CMU108-MF-50 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. The Authors thank Chao-Shih Chen for data analysis, and Professor Shiow-Lin Pan and the National Center for Genome Medicine, Ministry of Science and Technology of Taiwan, for technical support. The results published here are based in part on data generated by the HaploReg, 1000 Genomes, HapMap, and TCGA projects. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = jun,
day = "15",
doi = "10.1016/j.lfs.2021.119396",
language = "English",
volume = "275",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
}
