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Dietary aflatoxin B1 intake, genetic polymorphisms of CYP1A2, CYP2E1, EPHX1, GSTM1, and GSTT1, and gastric cancer risk in Korean

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Abstract

Purpose

We investigated the effects of aflatoxin B1 (AFB1) intake, genetic polymorphisms of AFB1 metabolic enzymes, and interactions between the polymorphisms and intake of AFB1 with regard to the risk of gastric cancer in Korean.

Methods

The participants in the study included 477 gastric cancer patients and 477 age- and sex-matched control subjects. Direct interviews and a structured questionnaire were used to determine the level of exposure to AFB1, and the GoldenGate assay and multiplex polymerase chain reaction were used for genotypic analyses of the cytochrome P450 1A2 (CYP1A2), cytochrome P450 1E1, epoxide hydrolase 1, and glutathione S-transferase genes.

Results

The probable daily intake of AFB1 was significantly higher among gastric cancer patients than among control subjects (cases vs. controls: 1.91 ± 0.87 vs. 1.65 ± 0.72 ng/kg bw/day, p < 0.0001), and increased AFB1 intake was significantly associated with an elevated risk of gastric cancer (odds ratio 1.94; 95 % confidence interval 1.43–2.63). However, genetic polymorphisms of AFB1 metabolic enzymes were not associated with gastric cancer, with the exception of CYP1A2. Moreover, there was no interaction between AFB1 intake and the genotypes of metabolic enzymes that affect gastric cancer risk.

Conclusions

Our results suggest that dietary AFB1 exposure might be associated with a risk of gastric cancer. However, the effect of AFB1 on gastric carcinogenesis may not be modulated by genetic polymorphisms of AFB1 metabolic enzymes.

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References

  1. The Korea Central Cancer Registry, National Cancer Center (2011) Annual report of cancer statistics in Korea in 2009. Ministry of Health and Welfare, Seoul

    Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917

    Article  PubMed  CAS  Google Scholar 

  3. Kim HJ, Chang WK, Kim MK, Lee SS, Choi BY (2002) Dietary factors and gastric cancer in Korea: a case-control study. Int J Cancer 97:531–535

    Article  PubMed  CAS  Google Scholar 

  4. Tsugane S, Sasazuki S (2007) Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer 10:75–83

    Article  PubMed  Google Scholar 

  5. Lee JK, Park BJ, Yoo KY, Ahn YO (1995) Dietary factors and stomach cancer: a case-control study in Korea. Int J Epidemiol 24:33–41

    Article  PubMed  CAS  Google Scholar 

  6. Kim HJ, Lee SS, Choi BY, Kim MK (2007) Nitrate intake relative to antioxidant vitamin intake affects gastric cancer risk: a case-control study in Korea. Nutr Cancer 59:185–191

    Article  PubMed  CAS  Google Scholar 

  7. Kim JH, Kim HY, Kim NY, Kim SW, Kim JG, Kim JJ, Roe IH, Seo JK, Sim JG, Ahn H, Yoon BC, Lee SW et al (2001) Seroepidemiological study of Helicobacter pylori infection in asymptomatic people in South Korea. J Gastroenterol Hepatol 16:969–975

    Article  PubMed  CAS  Google Scholar 

  8. Nan HM, Park JW, Song YJ, Yun HY, Park JS, Hyun T, Youn SJ, Kim YD, Kang JW, Kim H (2005) Kimchi and soybean pastes are risk factors of gastric cancer. World J Gastroenterol 21:3175–3181

    Google Scholar 

  9. Zhang YW, Eom SY, Kim YD, Song YJ, Yun HY, Park JS, Youn SJ, Kim BS, Kim H, Hein DW (2009) Effects of dietary factors and the NAT2 acetylator status on gastric cancer in Koreans. Int J Cancer 125:139–145

    Article  PubMed  CAS  Google Scholar 

  10. Ahn YO (1997) Diet and stomach cancer in Korea. Int J Cancer 10:7–9

    Article  PubMed  Google Scholar 

  11. Kim JH, Shin HS (1997) Effects of main raw material and jeot-kal (fermented fish sauce) on formation of N-nitrosamines during kimchi fermentation. J Food Hyg Safety 12:333–339

    Google Scholar 

  12. Seel DJ, Kawabata T, Nakamura M, Ishibashi T, Hamano M, Mashimo M, Shin SH, Sakamoto K, Jhee EC, Watanabe S (1994) N-nitroso compounds in two nitrosated food products in southwest Korea. Food Chem Toxicol 32:1117–1123

    Article  PubMed  CAS  Google Scholar 

  13. Ok HE, Kim HJ, Shim WB, Lee H, Bae DH, Chung DH, Chun HS (2007) Natural occurrence of aflatoxin B1 in marketed foods and risk estimates of dietary exposure in Koreans. J Food Prot 70:2824–2828

    PubMed  CAS  Google Scholar 

  14. Park JW, Kim EK, Kim YB (2004) Estimation of the daily exposure of Koreans to aflatoxin B1 through food consumption. Food Addit Contam 21:70–75

    Article  PubMed  CAS  Google Scholar 

  15. International Agency for Research on Cancer (1993) Aflatoxins. IARC Monogr Eval Carcinog Risks Hum 56:245–395

    Google Scholar 

  16. Guengerich FP, Johnson WW, Shimada T, Ueng YF, Yamazaki H, Langouet S (1998) Activation and detoxication of aflatoxin B1. Mutat Res 402:121–128

    Article  PubMed  CAS  Google Scholar 

  17. Guengerich FP, Johnson WW, Ueng YF, Yamazaki H, Shimada T (1996) Involvement of cytochrome P450, glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin B1 and relevance to risk of human liver cancer. Environ Health Perspect 104:557–562

    PubMed  CAS  Google Scholar 

  18. Wang JS, Groopman JD (1999) DNA damage by mycotoxins. Mutat Res 424:167–181

    Article  PubMed  CAS  Google Scholar 

  19. Bedard LL, Massey TE (2006) Aflatoxin B1-induced DNA damage and its repair. Cancer Lett 241:174–183

    Article  PubMed  CAS  Google Scholar 

  20. Tiemersma EW, Omer RE, Bunschoten A, van’t Veer P, Kok FJ, Idris MO, Kadaru AM, Fedail SS, Kampman E (2001) Role of genetic polymorphism of glutathione-S-transferase T1 and microsomal epoxide hydrolase in aflatoxin-associated hepatocellular carcinoma. Cancer Epidemiol Biomarkers Prev 10:785–791

    PubMed  CAS  Google Scholar 

  21. Long XD, Ma Y, Wei YP, Deng ZL (2006) The polymorphisms of GSTM1, GSTT1, HYL1*2, and XRCC1, and aflatoxin B1-related hepatocellular carcinoma in Guangxi population, China. Hepatol Res 36:48–55

    Article  PubMed  CAS  Google Scholar 

  22. Chen X, Wang H, Xie W, Liang R, Wei Z, Zhi L, Zhang X, Hao B, Zhong S, Zhou G, Zhang L, Gao X et al (2006) Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China. Pharmacogenet Genomics 16:219–227

    PubMed  CAS  Google Scholar 

  23. Kim MK, Lee SS, Ahn YO (1996) Reproducibility and validity of a self-administered semiquantitative food frequency questionnaire among middle-aged men in Seoul. Korean J Commun Nutrit 1:376–394

    Google Scholar 

  24. Thorn CF, Aklillu E, Klein TE, Altman RB (2012) PharmGKB summary: very important pharmacogene information for CYP1A2. Pharmacogenet Genomics 22:73–77

    Article  PubMed  CAS  Google Scholar 

  25. Zhou Q, Yu X, Shu C, Cai Y, Gong W, Wang X, Wang DM, Hu S (2011) Analysis of CYP3A4 genetic polymorphisms in Han Chinese. J Hum Genet 56:415–422

    Article  PubMed  CAS  Google Scholar 

  26. Liu F, Yuan D, Wei Y, Wang W, Yan L, Wen T, Xu M, Yang J, Li B (2012) Systematic review and meta-analysis of the relationship between EPHX1 polymorphisms and colorectal cancer risk. PLoS ONE 7:e43821. doi:10.1371/journal.pone.0043821

    Article  PubMed  CAS  Google Scholar 

  27. Wang X, Chorley BN, Pittman GS, Kleeberger SR, Brothers J 2nd, Liu G, Spira A, Bell DA (2010) Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer. PLoS ONE 5:e11934. doi:10.1371/journal.pone.0011934

    Article  PubMed  Google Scholar 

  28. Chen H, Sandler DP, Taylor JA, Shore DL, Liu E, Bloomfield CD, Bell DA (1996) Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect. Lancet 347:295–297

    Article  PubMed  CAS  Google Scholar 

  29. Purcell S, Cherny SS, Sham PC (2003) Genetic power calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149–150

    Article  PubMed  CAS  Google Scholar 

  30. Butler WH, Barnes JM (1966) Carcinoma of the glandular stomach in rats given diets containing aflatoxin. Nature 209:90

    Article  PubMed  CAS  Google Scholar 

  31. Larsson P, Tjalve H (1995) Extrahepatic bioactivation of aflatoxin B1 in fetal, infant and adult rats. Chem Biol Interact 94:1–19

    Article  PubMed  CAS  Google Scholar 

  32. Ma F, Misumi J, Zhao W, Aoki K, Kudo M (2003) Long-term treatment with sterigmatocystin, a fungus toxin, enhances the development of intestinal metaplasia of gastric mucosa in Helicobacter pylori-infected Mongolian gerbils. Scand J Gastroenterol 38:360–369

    Article  PubMed  CAS  Google Scholar 

  33. Misumi J (2004) The mechanisms of gastric cancer development produced by the combination of Helicobacter pylori with sterigmatocystin, a mycotoxin. Nippon Rinsho 62:1377–1386

    PubMed  Google Scholar 

  34. Kusunoki M, Misumi J, Shimada T, Aoki K, Matsuo N, Sumiyoshi H, Yamaguchi T, Yoshioka H (2011) Long-term administration of the fungus toxin, sterigmatocystin, induces intestinal metaplasia and increases the proliferative activity of PCNA, p53, and MDM2 in the gastric mucosa of aged Mongolian gerbils. Environ Health Prev Med 16:224–231

    Article  PubMed  CAS  Google Scholar 

  35. Codex Alimentarius Commission (1995) Codex general standard for contaminants and toxins in food and feed, CODEX STAN 193-1995. http://www.codexalimentarius.net/input/download/standards/17/CXS_193e.pdf. Accessed 16 July 2013

  36. Wu AH, Yang D, Pike MC (2000) A meta-analysis of soyfoods and risk of stomach cancer: the problem of potential confounders. Cancer Epidemiol Biomarkers Prev 9:1051–1058

    PubMed  CAS  Google Scholar 

  37. Li FQ, Yoshizawa T, Kawamura O, Luo XY, Li YW (2001) Aflatoxins and fumonisins in corn from the high-incidence area for human hepatocellular carcinoma in Guangxi, China. J Agric Food Chem 49:4122–4126

    Article  PubMed  CAS  Google Scholar 

  38. Qian GS, Ross RK, Yu MC, Yuan JM, Gao YT, Henderson BE, Wogan GN, Groopman JD (1994) A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People’s Republic of China. Cancer Epidemiol Biomarkers Prev 3:3–10

    PubMed  CAS  Google Scholar 

  39. Eaton DA, Gallagher EP, Bammler TK, Kunxe KL (1995) Role of cytochrome P450 1A2 in chemical carcinogenesis: implications for human variability in expression and enzyme activity. Pharmacogenetic 5:259–274

    Article  CAS  Google Scholar 

  40. Boobis AR, Lynch AM, Murray S (1994) CYP1A2-catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans. Cancer Res 54:89–94

    PubMed  CAS  Google Scholar 

  41. Tatemichi M, Nomura S, Ogura T, Sone H, Nagata H, Esumi H (1999) Mutagenic activation of environmental carcinogens by microsomes of gastric mucosa with metaplasia. Cancer Res 59:3893–3898

    PubMed  CAS  Google Scholar 

  42. Agudo A, Sala N, Pera G, Capellá G, Berenguer A, García N, Palli D, Boeing H, Del Giudice G, Saieva C, Carneiro F, Berrino F et al (2006) Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 15:2427–2434

    Article  PubMed  CAS  Google Scholar 

  43. Ikeda S, Sasazuki S, Natsukawa S, Shaura K, Koizumi Y, Kasuga Y, Ohnami S, Sakamoto H, Yoshida T, Iwasaki M, Tsugane S (2008) Screening of 214 single nucleotide polymorphisms in 44 candidate cancer susceptibility genes: a case-control study on gastric and colorectal cancers in the Japanese population. Am J Gastroenterol 103:1476–1487

    Article  PubMed  CAS  Google Scholar 

  44. Kobayashi M, Otani T, Iwasaki M, Natsukawa S, Shaura K, Koizumi Y, Kasuga Y, Sakamoto H, Yoshida T, Tsugane S (2009) Association between dietary heterocyclic amine levels, genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 and risk of stomach cancer: a hospital-based case-control study in Japan. Gastric Cancer 12:198–205

    Article  PubMed  CAS  Google Scholar 

  45. Ghotbi R, Christensen M, Roh HK, Ingelman-Sundberg M, Aklillu E, Bertilsson L (2007) Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans. Eur J Clin Pharmacol 63:537–546

    Article  PubMed  CAS  Google Scholar 

  46. Takata K, Saruwatari J, Nakada N, Nakagawa M, Fukuda K, Tanaka F, Takenaka S, Mihara S, Marubayashi T, Nakagawa K (2006) Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy. Eur J Clin Pharmacol 62:23–28

    Article  PubMed  CAS  Google Scholar 

  47. Wu MS, Chen CJ, Lin MT, Wang HP, Shun CT, Sheu JC, Lin JT (2002) Genetic polymorphisms of cytochrome p450 2E1, glutathione S-transferase M1 and T1, and susceptibility to gastric carcinoma in Taiwan. Int J Colorectal Dis 17:338–343

    Article  PubMed  Google Scholar 

  48. Wideroff L, Vaughan TL, Farin FM, Gammon MD, Risch H, Stanford JL, Chow WH (2007) GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas. Cancer Detect Prev 31:233–236

    Article  PubMed  CAS  Google Scholar 

  49. Kato S, Onda M, Matsukura N, Tokunaga A, Matsuda N, Yamashita K, Shields PG (1996) Genetic polymorphisms of the cancer related gene and Helicobacter pylori infection in Japanese gastric cancer patients. An age and gender matched case-control study. Cancer 77:1654–1661

    PubMed  CAS  Google Scholar 

  50. Deakin M, Elder J, Hendrickse C, Peckham D, Baldwin D, Pantin C, Wild N, Leopard P, Bell DA, Jones P, Duncan H, Brannigan K et al (1996) Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis 17:881–884

    Article  PubMed  CAS  Google Scholar 

  51. Hong SH, Kim JW, Kim HG, Park IK, Ryoo JW, Lee CH, Sohn YK, Lee JY (2006) Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and N-acetyltransferase 2 polymorphisms and the risk of gastric cancer. J Prev Med Public Health 39:135–140

    PubMed  Google Scholar 

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Acknowledgments

This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1120330).

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Correspondence to Heon Kim.

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Eom, SY., Yim, DH., Zhang, Y. et al. Dietary aflatoxin B1 intake, genetic polymorphisms of CYP1A2, CYP2E1, EPHX1, GSTM1, and GSTT1, and gastric cancer risk in Korean. Cancer Causes Control 24, 1963–1972 (2013). https://doi.org/10.1007/s10552-013-0272-3

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