Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts
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AbstractGermline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a two‐phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome‐wide genotypes at 246 173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazard regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta‐analysis of all samples (n = 5553) confirms that the presence of rs1131636‐T, located in the 3′‐UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20–1.47, P = 6.31 × 10−8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promotes the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR‐1253 is identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.
All Author(s) ListGuo YM, Chen JR, Feng YC, Chua MLK, Zeng YN, Hui EP, Chan AKC, Tang LQ, Wang L, Cui Q, Han HQ, Luo CL, Lin GW, Liang Y, Liu Y, He ZL, Liu YX, Wei PP, Liu CJ, Peng W, Han BW, Zuo XY, Ong EHW, Yeo ELL, Low KP, Tan GS, Lim TKH, Hwang JSG, Li B, Feng QS, Xia XJ, Xia YF, Ko J, Dai W, Lung ML, Chan ATC, Lo DYM, Zeng MS, Mai HQ, Liu JJ, Zeng YX, Bei JX
Journal nameAdvanced Science
Year2020
Month5
Day20
Volume Number7
Issue Number10
PublisherWILEY
Article number1903727
ISSN2198-3844
eISSN2198-3844
LanguagesEnglish-United Kingdom
Keywordsbiomarkers, cancer prognosis, germline polymorphisms, nasopharyngeal carcinoma, RPA1, single nucleotide polymorphisms
Web of Science Subject CategoriesChemistry, Multidisciplinary;Nanoscience & Nanotechnology;Materials Science, Multidisciplinary;Chemistry;Science & Technology - Other Topics;Materials Science

Last updated on 2021-20-06 at 23:57