Brief Article
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World J Gastroenterol. Mar 21, 2013; 19(11): 1778-1787
Published online Mar 21, 2013. doi: 10.3748/wjg.v19.i11.1778
Evaluation of the relationship between dietary factors, CagA-positive Helicobacter pylori infection, and RUNX3 promoter hypermethylation in gastric cancer tissue
Yan-Wei Zhang, Sang-Yong Eom, Dong-Hyuk Yim, Young-Jin Song, Hyo-Yung Yun, Joo-Seung Park, Sei-Jin Youn, Byung-Sik Kim, Yong-Dae Kim, Heon Kim
Yan-Wei Zhang, Sang-Yong Eom, Dong-Hyuk Yim, Yong-Dae Kim, Heon Kim, Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea
Young-Jin Song, Hyo-Yung Yun, Department of Surgery, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea
Joo-Seung Park, Department of Surgery, College of Medicine, Eulji University, Daejon 461-713, South Korea
Sei-Jin Youn, Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea
Byung-Sik Kim, Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University, Seoul 138-736, South Korea
Author contributions: Zhang YW and Kim H designed the study protocol; Eom SY and Yim DH performed the statistical analysis and data interpretation; Song YJ, Yun HY, Park JS, Youn SJ and Kim BS equally contributed to this study by selection of subjects, interviews, cancer tissue sampling and clinical data acquisition; Zhang YW and Kim YD drafted the manuscript.
Supported by A Grant from 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: October 10, 2012
Revised: January 4, 2013
Accepted: January 17, 2013
Published online: March 21, 2013
Abstract

AIM: To evaluate the relationship among Helicobacter pylori (H. pylori) infection, CagA status, and dietary factors with RUNX3 promoter hypermethylation.

METHODS: Gastric cancer tissue samples were collected from 184 South Korean patients. All patients were interviewed following a semi-quantitative food frequency questionnaire. The average frequencies of intake and portion sizes of 89 common food items were documented, and total intakes of calories, nutrients, vitamins, and minerals were calculated for each subject. DNA was extracted from gastric cancer tissue samples, and amplification of the HSP60 gene was performed to detect H. pylori infection. Nested polymerase chain reaction (PCR) was used to detect the presence of the CagA gene. RUNX3 gene expression was measured by reverse transcription-PCR, and RUNX3 methylation status was evaluated by methylation-specific PCR. The odds ratios (ORs) and 95%CI associated with RUNX3 promoter hypermethylation status were estimated for each of the food groups, lifestyle factors, and the interaction between dietary and lifestyle factors with CagA status of H. pylori infection.

RESULTS: Overall, 164 patients (89.1%) were positive for H. pylori DNA, with the CagA gene detected in 59 (36%) of these H. pylori-positive samples. In all, 106 (57.6%) patients with gastric cancer demonstrated CpG island hypermethylation at the RUNX3 promoter. RUNX3 expression was undetectable in 52 (43.7%) of the 119 gastric cancer tissues sampled. A high consumption of eggs may increase the risk of RUNX3 methylation in gastric cancer patients, having a mean OR of 2.15 (range, 1.14-4.08). A significantly increased OR of 4.28 (range, 1.19-15.49) was observed with a high consumption of nuts in patients with CagA-positive H. pylori infection. High intakes of carbohydrate, vitamin B1, and vitamin E may decrease the risk of RUNX3 methylation in gastric cancer tissue, particularly in CagA- or H. pylori-negative infection, with OR of 0.41 (0.19-0.90), 0.42 (0.20-0.89), and 0.29 (0.13-0.62), respectively. A high consumption of fruits may protect against RUNX3 methylation.

CONCLUSION: These results suggest that the CagA status of H. pylori infection may be a modifier of dietary effects on RUNX3 methylation in gastric cancer tissue.

Keywords: Gastric cancer, RUNX3, Helicobacter pylori, CagA, Dietary factors