Brief Article
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World J Gastroenterol. Mar 14, 2014; 20(10): 2688-2694
Published online Mar 14, 2014. doi: 10.3748/wjg.v20.i10.2688
Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans
Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Yong-Ge Ze, Zha-Xi Bianba, Cuo-Mu Ciren, Yu-Qiang Nie
Kang Li, Zeng Dan, Xue-Jun Hu, Luo-Bu Gesang, Department of Gastroenterology, People’s Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China
Yong-Ge Ze, Zha-Xi Bianba, Cuo-Mu Ciren, Department of Oncology, People’s Hospital of Tibet Autonomous Region, Lhasa 850000, Tibet Autonomous Region, China
Yu-Qiang Nie, Department of Gastroenterology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong Province, China
Author contributions: Li K, Dan Z, Hu XJ and Gesang LB contributed equally to this work; Li K, Dan Z, Hu XJ, Gesang LB and Nie YQ designed the study; Li K, Ze YG, Bianba ZX and Ciren CM performed the research; Hu XJ and Gesang LB analyzed the data; Li K, Dan Z and Nie YQ wrote the manuscript.
Supported by National Natural Science Foundation of China, No. 81060165
Correspondence to: Dr. Kang Li, Department of Gastroenterology, People’s Hospital of Tibet Autonomous Region, 18 North Lin Kuo Road, Lhasa 850000, Tibet Autonomous Region, China. likang820@aliyun.com
Telephone: +86-891-6333324 Fax: +86-891-6371511
Received: August 29, 2013
Revised: November 28, 2013
Accepted: January 2, 2014
Published online: March 14, 2014
Abstract

AIM: To investigate the relationship between CD14-260 and -651 polymorphisms and the risk of developing gastric cancer.

METHODS: DNA was extracted from peripheral blood samples obtained from 225 Tibetans with gastric cancer and 237 healthy Tibetans, and analyzed using the polymerase chain reaction/ligase detection (PCR/LDR) method to determine the genotypes at -260 and -651 loci of the CD14 promoter. The allele frequencies, genotype frequencies, and haplotypes were analyzed for their association with gastric cancer risk using online SHEsis software. The luciferase reporter assay and point mutation analysis were used to construct in vitro plasmids expressing a C/T homozygote at the -260 locus of the CD14 promoter.

RESULTS: The frequencies of CC, CT and TT genotypes in the CD14-260 C/T locus in gastric cancer patients were 19.1%, 38.7% and 42.2%, respectively, whereas they were 33.3%, 32.5% and 34.2%, respectively, in healthy control subjects. CT genotype carriers were more frequently found among gastric cancer patients than healthy controls (OR = 2.076; 95%CI: 1.282-3.360). Also, TT genotype carriers were more frequently found among gastric cancer patients (OR = 2.155; 95%CI: 1.340-3.466). Compared to the C allele of CD14/-260, the T allele was associated with an increased risk for gastric cancer (OR = 1.574; 95%CI: 1.121-2.045). Furthermore, the frequencies of CC, CT and TT in the CD14-651 C/T locus in gastric cancer patients were 64.4%, 29.3% and 6.2%, respectively, while they were 56.5%, 35.0% and 8.4%, respectively, in the healthy control subjects (P > 0.05). Data obtained using the luciferase reporter assay showed that the p260T homozygote was associated with greater CD14 promoter activity (P < 0.01).

CONCLUSION: CD14/-260 polymorphism is associated with gastric cancer risk in Highland Tibetans and affects CD14 promoter activity, thereby regulating CD14 expression.

Keywords: CD14, Single nucleotide polymorphisms, Cancer susceptibility, Gastric cancer, Tibetans

Core tip: This is the first study to report that CD14 gene polymorphisms in Highland Tibetans are associated with gastric cancer risk. We also identified a biomarker that can be used in gastric cancer research and clinical practice.