Case Control Study
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World J Gastroenterol. Jul 14, 2014; 20(26): 8592-8598
Published online Jul 14, 2014. doi: 10.3748/wjg.v20.i26.8592
Risk of gastric cancer is associated with PRKAA1 gene polymorphisms in Koreans
Yong-Dae Kim, Dong-Hyuk Yim, 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, Hee Kwan Won, Heon Kim
Yong-Dae Kim, Dong-Hyuk Yim, Sang-Yong Eom, Sun In Moon, Heon Kim, Department of Preventive Medicine, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea
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 301-832, South Korea
Byung Sik Kim, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University, Seoul 138-736, South Korea
Jong-Young Lee, Center for Genome Science, National Institute of Health, Cheongju 363-951, South Korea
Hee Kwan Won, Department of Internal Medicine, Division of Endocrinology and Metabolism, School of Medicine, Konyang University, Daejeon 302-718, South Korea
Author contributions: Kim YD, Lee JY, and Kim H designed the study protocol; Yim DH, Eom SY, and Moon SI performed the statistical analysis and data interpretation; Song YJ, Yun HY, Park JS, Youn SJ, Kim BS, Won HK and Hyun T contributed equally to this study through the selection of subjects, sampling, and clinical data acquisition; Kim YD and Kim H drafted the manuscript.
Supported by A grant from the National R & D Program for Cancer Control, Ministry of Health and Welfare, South Korea, No. 1120330
Correspondence to: Heon Kim, Professor, Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, 52 Naesudong-ro, Hungdok-gu, Cheongju 361-763, South Korea. kimheon@cbu.ac.kr
Telephone: +82-43-2612864 Fax: +82-43-2742965
Received: December 24, 2013
Revised: January 29, 2014
Accepted: April 2, 2014
Published online: July 14, 2014
Processing time: 202 Days and 7.3 Hours
Abstract

AIM: To evaluate the association between genetic polymorphisms of the gene encoding AMP-activated protein kinase (PRKAA1) and the risk of gastric cancer.

METHODS: The study subjects consisted of 477 age- and sex-matched case-control pairs. Genotyping was performed for 5 tag single nucleotide polymorphisms (SNPs): rs13361707, rs154268, rs3805486, rs6882903, and rs10074991. Associations between gastric cancer and putative risk factors (including the SNPs) were analyzed with multivariate conditional logistic regression models, after adjusting for potential confounding factors. Multiple testing corrections were implemented following methodology for controlling the false discovery rate. Gene-based association tests were performed by using the versatile gene-based association study (VEGAS) method.

RESULTS: In the dominant model, SNPs rs13361707 [odds ratio (OR) = 1.51, 95%CI: 1.07-2.11)], rs154268 (OR = 1.65, 95%CI: 1.22-2.22), rs6882903 (OR = 1.48, 95%CI: 1.09-2.00), and rs10074991 (OR = 1.53, 95%CI: 1.09-2.16) were significantly associated with an increased risk of gastric cancer. In the recessive model, SNPs rs154268 (OR = 1.66, 95%CI: 1.22-2.26), rs3805486 (OR = 0.63, 95%CI: 0.46-0.85), and rs10074991 (OR = 1.47, 95%CI: 1.15-1.88) were significant risk or protective factors for gastric cancer. In the codominant model, the ORs of each of the 5 SNPs were statistically significant. All SNPs in the model showed a dose-response relationship between the minor allele frequency and the risk of gastric cancer. Most notably, subjects with a homozygous minor allele in SNP rs10074991 showed 2.15 times the risk of gastric cancer as subjects without a minor allele. The PRKAA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.

CONCLUSION: All 5 tested tag SNPs of the PRKAA1 gene (rs13361707, rs154268, rs3805486, rs6882903, and rs10074991) were significantly associated with gastric cancer.

Keywords: AMP-activated protein kinase; Gastric cancer; PRKAA1; Single nucleotide polymorphism; Case-control study

Core tip: There were a few studies to evaluate association between PRKAA1 gene and gastric cancer. However, in previous study, only one single nucleotide polymorphism (SNP) (rs13361707) of PRKAA1 gene was focused. The purpose of this study was to evaluate the association between 5 SNPs of the gene encoding AMP-activated protein kinase (PRKAA1) and the risk of gastric cancer. All SNPs in the model showed a dose-response relationship between the minor allele frequency and the risk of gastric cancer. The PRKAA1 gene showed a significant gene-based association with gastric cancer in the versatile gene-based association study test.