Tian Tian1,2, Ling Xiao2, Jiangbo Du2,3, Xun Zhu2, Yayun Gu2, Na Qin2, Caiwang Yan2, Li Liu4, Hongxia Ma2,3, Yue Jiang2,3, Jiaping Chen2,3, Hao Yu5, Juncheng Dai6,7. 1. Department of Epidemiology and Biostatistics, School of Public Health, Nantong University, Nantong, 226019, China. 2. Department of Epidemiology and Biostatistics, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. 3. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China. 4. Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University and Jiangsu Province Hospital, Nanjing, China. 5. Department of Epidemiology and Biostatistics, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. haoyu@njmu.edu.cn. 6. Department of Epidemiology and Biostatistics, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. djc@njmu.edu.cn. 7. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China. djc@njmu.edu.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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