Polymorphisms in CARS are associated with gastric cancer risk: a two-stage case–control study in the Chinese population
The cysteinyl transfer RNA synthetase gene (CARS) is located on chromosome band 11p15.5, which is an important tumor-suppressor gene region. Mutations in CARS have been identified in many kinds of cancers; however, evidence for a relationship between genetic variants in CARS and gastric cancer at the population level is still lacking. Thus, we explored the association of variants in CARS with gastric cancer using a two-stage case–control strategy in Chinese.
We undertook a two-stage case–control study to investigate the association between polymorphisms in CARS and risk of gastric cancer with use of an Illumina Infinium® BeadChip and an ABI 7900 system.
Four single nucleotide polymorphisms (SNPs) were significantly associated with gastric cancer risk in both the discovery stage and the validation stage after adjustment for age and sex. In addition, the combined results of the two stages showed these SNPs were related to gastric cancer risk (P false discovery rate ≤ 0.001 for rs384,490, rs729662, rs2071101, and rs7394702). In silico analyses revealed that rs384490 and rs7394702 could affect transcription factor response elements or DNA methylation of CARS, and rs729662 was associated with the prognosis of gastric cancer. Additionally, expression quantitative trait loci analysis showed rs384490 and rs729662 might alter expression of CARS-related genes.
The potential functional SNPs in CARS might influence the biological functions of CARS or CARS-related genes and ultimately modify the occurrence and development of gastric cancer in Chinese. Further large-scale population-based studies or biological functional assays are warranted to validate our findings.
KeywordsGastric cancer Susceptibility CARS Polymorphism Genetic association
This work was funded by National Natural Science of China (81521004, 81230067, 81573238, 81422042, 81373090, 81302107), the Science Foundation for Distinguished Young Scholars of Jiangsu (BK20130042), Excellent Youth Foundation of Jiangsu (BK20160095), Jiangsu Province Clinical Science and Technology Projects (BL2012008), Key Grant of Natural Science Foundation of Jiangsu Higher Education Institutions (15KJA330002), the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine) and the Top-Notch Academic Programs Project of Jiangsu Higher Education Institution. The authors thank all study participants, research staff, and students who participated in this work.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human rights statement
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.
Informed consent was obtained from all patients for their being included in the study.
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