Functional polymorphisms in circadian positive feedback loop genes predict postsurgical prognosis of gastric cancer

Autor: Falin Qu, Yibing Chen, Dandan Wang, Zhihui Jiao, Xiaofei Zhang, Wei Du, Juqin Dong, Lin Lü, Zhengzhi Zou, Yucen Song
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
CLOCK Proteins
Kaplan-Meier Estimate
circadian gene
0302 clinical medicine
Genotype
Basic Helix-Loop-Helix Transcription Factors
Promoter Regions
Genetic
Original Research
NPAS2
Circadian Rhythm Signaling Peptides and Proteins
ARNTL Transcription Factors
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Gene Expression Regulation
Neoplastic
CLOCK
030220 oncology & carcinogenesis
Female
Cancer Prevention
China
medicine.medical_specialty
single‐nucleotide polymorphism
Nerve Tissue Proteins
Single-nucleotide polymorphism
Biology
Polymorphism
Single Nucleotide
lcsh:RC254-282
03 medical and health sciences
Stomach Neoplasms
Circadian Clocks
Internal medicine
medicine
Humans
SNP
Genetic Predisposition to Disease
Radiology
Nuclear Medicine and imaging
Allele
Aged
Proportional hazards model
gastric cancer
Cancer
Epistasis
Genetic
medicine.disease
030104 developmental biology
prognosis
Zdroj: Cancer Medicine, Vol 8, Iss 4, Pp 1919-1929 (2019)
Cancer Medicine
ISSN: 2045-7634
DOI: 10.1002/cam4.2050
Popis: Background Circadian positive feedback loop (CPFL) genes (CLOCK, BAML1, and NPAS2) have been implicated in cancer initiation and progression. The purpose of this study was to explore the effects of single‐nucleotide polymorphisms (SNPs) in CPFL genes on prognosis of gastric cancer (GC) patients. Methods Nine functional SNPs from the three CPFL genes were genotyped in a cohort of 704 GC patients undergoing resection. Multivariate Cox regression model and Kaplan‐Meier curve were used for prognosis analysis. Results Among the nine SNPs, rs11133399 in CLOCK, rs1044432 and rs2279284 in BAML1 were significantly associated with GC overall survival and recurrence‐free survival. The unfavorable genotypes of these SNPs showed a cumulative effect on GC prognosis. Multivariate assessment model indicated that these SNPs, in conjunction with clinical variables, enhanced the power to predict GC prognosis. In addition, survival tree analysis revealed the genotype of rs11133399 as a primary risk factor contributing to the prognosis of GC patients. Functional assays showed that the G allele in rs11133399 significantly enhanced luciferase reporter activity than A allele. Immunohistochemical analysis further demonstrated that the genotype of rs11133399 was significantly associated with the expression level of CLOCK in GC tissues, suggesting that this SNP might affect the prognosis of GC through its influence on the expression of CLOCK gene. Conclusions Our data indicate that SNPs in CPFL genes might contribute to the clinical outcome of GC through their impact on gene expression. Further studies are needed to elucidate its underlying molecular mechanisms.
Databáze: OpenAIRE
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