Brief Article
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World J Gastroenterol. Sep 21, 2013; 19(35): 5870-5876
Published online Sep 21, 2013. doi: 10.3748/wjg.v19.i35.5870
ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population
Dong-Hyuk Yim, Yan-Wei Zhang, Sang-Yong Eom, Sun In Moon, Hyo-Yung Yun, Young-Jin Song, Sei-Jin Youn, Taisun Hyun, Joo-Seung Park, Byung Sik Kim, Jong-Young Lee, Yong-Dae Kim, Heon Kim
Dong-Hyuk Yim, Sang-Yong Eom, Sun In Moon, Yong-Dae Kim, Heon Kim, Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea
Yan-Wei Zhang, Key Laboratory of Molecular Biology of Guangdong Province, Center for Disease Control and Prevention, Shenzhen 518020, Guangdong Province, China
Hyo-Yung Yun, Young-Jin Song, Department of Surgery, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea
Sei-Jin Youn, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea
Taisun Hyun, Department of Food and Nutrition, Chungbuk National University, Cheongju 361-763, South Korea
Joo-Seung Park, Department of Surgery, College of Medicine, Eulji University, Daejon 301-746, South Korea
Byung Sik Kim, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University, Seoul 680-749, South Korea
Jong-Young Lee, Center for Genome Science, National Institute of Health, Chungcheongbuk-do 363-951, South Korea
Author contributions: Lee JY, Kim YD and Kim H designed the study protocol; Eom SY, Yim DH, Moon SI and Zhang YW performed the statistical analysis and data interpretation; Song YJ, Yun HY, Park JS, Youn SJ, Kim BS and Hyun T contributed equally to this study through the selection of subjects, sampling, and clinical data acquisition; Yim DH, Kim YD and Kim H drafted the manuscript.
Supported by The National R and D Program for Cancer Control, Ministry of Health and Welfare, South Korea, No. 1120330
Correspondence to: Dr. Heon Kim, Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, 52 Naesudong-ro, Hungdok-gu, Cheongju, Chungbuk 361-763, South Korea. kimheon@cbu.ac.kr
Telephone: +82-43-2612864 Fax: +82-43-2742965
Received: April 4, 2013
Revised: July 15, 2013
Accepted: August 4, 2013
Published online: September 21, 2013
Abstract

AIM: To evaluate the association between the genetic polymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.

METHODS: The study subjects were 477 age- and sex-matched case-control pairs. Genotyping was performed for 15 single nucleotide polymorphisms (SNPs) in ITGA1. The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models. Multiple testing corrections were carried out following methodology for controlling the false discovery rate. Gene-based association tests were performed using the versatile gene-based association study (VEGAS) method.

RESULTS: In the codominant model, the ORs for SNPs rs2432143 (1.517; 95%CI: 1.144-2.011) and rs2447867 (1.258; 95%CI: 1.051-1.505) were statistically significant. In the dominant model, polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors, with ORs of 1.337 (95%CI: 1.029-1.737) and 1.412 (95%CI: 1.061-1.881), respectively. In the recessive model, only the rs2432143 polymorphism was significant (OR = 1.559, 95%CI: 1.150-2.114). The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model (OR = 0.602, 95%CI: 0.212-0.709, P = 0.021) and the dominant model (OR = 0.653, 95%CI: 0.483-0.884). The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test. In the dominant model, the A-T type of ITGA1 haplotype block 2 was a significant risk factor (OR = 1.341, 95%CI: 1.034-1.741). SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and, thus, to the risk of developing gastric cancer.

CONCLUSION: ITGA1 gene SNPs rs1862610, rs24321

43, and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.

Keywords: Integrin, ITGA1, Gastric cancer, Polymorphism, Haplotype

Core tip: There are few studies addressing the role of the integrin α 1 subunit in the development of gastric cancer. To the best of our knowledge, this study is the first to show that ITGA1 gene single nucleotide polymorphisms and haplotypes are associated with gastric cancer risk.