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Association between Helicobacter pylori infection and liver cancer mortality in 67 rural Chinese counties

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Abstract

Background

Although a growing body of evidence from experimental and clinical studies suggests that Helicobacter pylori may play a role in liver cancer etiology, few epidemiologic studies have investigated this hypothesis.

Methods

Liver cancer mortality rates in 1986–1988 for the 67 Chinese counties were obtained from a nationwide survey among subjects aged 35–69 years. Blood samples were collected from selected individuals of the similar age range in the same 67 counties in 1989. H. pylori infection was evaluated by measuring its antibodies (IgG) in plasma samples using an enzyme-linked immunosorbent assay (ELISA). Pearson correlation and multiple regression analyses were performed to test our hypothesis.

Results

Prevalence rates of H. pylori infection were positively correlated with liver cancer mortality in both men (r = 0.43, p = 0.0002) and women (r = 0.41, p = 0.0005). This significant association persisted after adjustment for body mass index, income, cigarette smoking, alcohol consumption, HBsAg positivity, diabetes mortality, and salt-preserved vegetable intake. Stratified analysis revealed suggestive interactions of H. pylori prevalence with HBsAg positivity and urinary aflatoxin M1 in men in relation to liver cancer mortality.

Conclusion

The present study offers novel epidemiologic evidence suggesting that infection with H. pylori is associated with an increased risk of death from liver cancer among rural Chinese residents.

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References

  1. AdC Romero, Baroni Ferreira TR, dos Santos Dias CT, Calori-Domingues MA, da Gloria EM (2010) Occurrence of AFM(1) in urine samples of a Brazilian population and association with food consumption. Food Control 21:554–558

    Article  Google Scholar 

  2. Avenaud P, Marais A, Monteiro L, Le Bail B, Bioulac Sage P, Balabaud C, Megraud F (2000) Detection of Helicobacter species in the liver of patients with and without primary liver carcinoma. Cancer 89:1431–1439

    Article  PubMed  CAS  Google Scholar 

  3. Berasain C, Castillo J, Perugorria MJ, Latasa MU, Prieto J, Avila MA (2009) Inflammation and liver cancer: new molecular links. Ann N Y Acad Sci 1155:206–221

    Article  PubMed  CAS  Google Scholar 

  4. Boonyanugomol W, Chomvarin C, Baik SC, Song JY, Hahnvajanawong C, Kim KM, Cho MJ, Lee WK, Kang HL, Rhee KH, Sripa B (2011) Role of cagA-positive Helicobacter pylori on cell proliferation, apoptosis, and inflammation in biliary cells. Dig Dis Sci 56:1682–1692

    Article  PubMed  Google Scholar 

  5. Cellini L, Allocati N, Piattelli A, Petrelli I, Fanci P, Dainelli B (1995) Microbiological evidence of Helicobacter pylori from dental plaque in dyspeptic patients. New Microbiol 18:187–192

    PubMed  CAS  Google Scholar 

  6. Chen NL, Bai L, Deng T, Zhang C, Kong QY, Chen H (2004) Expression of hepatitis B virus antigen and Helicobacter pylori infection in gastric mucosa of patients with chronic liver disease. Hepatobiliary Pancreat Dis Int 3:223–225

    PubMed  CAS  Google Scholar 

  7. Chen J, Peto R, Pan W, Liu B, Campbell T, Boreham J, Parpia B, Cassano P, Chen Z (2006) Mortality, biochemistry, diet and lifestyle in rural China: geographic study of the characteristics of 69 counties in Mainland China and 16 areas in Taiwan. Oxford University Press, Oxford

    Google Scholar 

  8. Cochrane J, Chen H, Conigrave KM, Hao W (2003) Alcohol use in China. Alcohol Alcohol 38:537–542

    Article  PubMed  Google Scholar 

  9. Coppola N, De Stefano G, Marrocco C, Scarano F, Scolastico C, Tarantino L, Rossi G, Battaglia M, Onofrio M, D’Aniello F, Pisapia R, Sagnelli C, Sagnelli E, Piccinino F, Giorgio A, Filippini P (2003) Helicobacter spp. and liver diseases. Infez Med 11:201–207

    PubMed  Google Scholar 

  10. Correa P (1997) Helicobacter pylori and the cell cycle. J Natl Cancer Inst 89:836–837

    Article  PubMed  CAS  Google Scholar 

  11. Dore MP, Realdi G, Mura D, Graham DY, Sepulveda AR (2002) Helicobacter infection in patients with HCV-related chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Dig Dis Sci 47:1638–1643

    Article  PubMed  Google Scholar 

  12. Egner PA, Wang JB, Zhu YR, Zhang BC, Wu Y, Zhang QN, Qian GS, Kuang SY, Gange SJ, Jacobson LP, Helzlsouer KJ, Bailey GS, Groopman JD, Kensler TW (2001) Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci U S A 98:14601–14606

    Article  PubMed  CAS  Google Scholar 

  13. El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576

    Article  PubMed  CAS  Google Scholar 

  14. Fan XG, Peng XN, Huang Y, Yakoob J, Wang ZM, Chen YP (2002) Helicobacter species ribosomal DNA recovered from the liver tissue of Chinese patients with primary hepatocellular carcinoma. Clin Infect Dis 35:1555–1557

    Article  PubMed  CAS  Google Scholar 

  15. Ferguson DA Jr, Li C, Patel NR, Mayberry WR, Chi DS, Thomas E (1993) Isolation of Helicobacter pylori from saliva. J Clin Microbiol 31:2802–2804

    PubMed  Google Scholar 

  16. Fox JG, Dewhirst FE, Tully JG, Paster BJ, Yan L, Taylor NS, Collins MJ Jr, Gorelick PL, Ward JM (1994) Helicobacter hepaticus sp. nov., a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice. J Clin Microbiol 32:1238–1245

    PubMed  CAS  Google Scholar 

  17. Fox JG, Yan LL, Dewhirst FE, Paster BJ, Shames B, Murphy JC, Hayward A, Belcher JC, Mendes EN (1995) Helicobacter bilis sp. nov., a novel Helicobacter species isolated from bile, livers, and intestines of aged, inbred mice. J Clin Microbiol 33:445–454

    PubMed  CAS  Google Scholar 

  18. Fox JG, Drolet R, Higgins R, Messier S, Yan L, Coleman BE, Paster BJ, Dewhirst FE (1996) Helicobacter canis isolated from a dog liver with multifocal necrotizing hepatitis. J Clin Microbiol 34:2479–2482

    PubMed  CAS  Google Scholar 

  19. Gao S, Yang WS, Zhang W, Gao J, Xiang YB (2010) Analysis and comparison of population-based survival rates of patients with primary liver cancer worldwide. Tumor 30:1027–1034

    Google Scholar 

  20. Guan Y (1993) A study on the relationship between Helicobacter pylori and chronic gastritis and peptic ulcer by the case-control method and sequential analysis. Zhonghua Liu Xing Bing Xue Za Zhi 14:75–77

    PubMed  CAS  Google Scholar 

  21. Huang Y, Fan XG, Zhou JH (2004) Immunohistochemistry of Helicobacter pylori in primary liver carcinoma tissues. Zhong Nan Da Xue Xue Bao Yi Xue Ban 29:15–17

    PubMed  CAS  Google Scholar 

  22. Huang Y, Fan XG, Wang ZM, Zhou JH, Tian XF, Li N (2004) Identification of Helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol 57:1273–1277

    Article  PubMed  CAS  Google Scholar 

  23. Ito K, Nakamura M, Toda G, Negishi M, Torii A, Ohno T (2004) Potential role of Helicobacter pylori in hepatocarcinogenesis. Int J Mol Med 13:221–227

    PubMed  CAS  Google Scholar 

  24. Ito K, Yamaoka Y, Yoffe B, Graham DY (2008) Disturbance of apoptosis and DNA synthesis by Helicobacter pylori infection of hepatocytes. Dig Dis Sci 53:2532–2540

    Article  PubMed  CAS  Google Scholar 

  25. Konturek JW (2003) Discovery by Jaworski of Helicobacter pylori and its pathogenetic role in peptic ulcer, gastritis and gastric cancer. J Physiol Pharmacol 54(Suppl 3):23–41

    PubMed  Google Scholar 

  26. Liu Y, Chang CC, Marsh GM, Wu F (2012) Population attributable risk of aflatoxin-related liver cancer: systematic review and meta-analysis. Eur J Cancer 48:2125–2136

    Article  PubMed  Google Scholar 

  27. Mahady GB, Pendland SL, Stoia A, Hamill FA, Fabricant D, Dietz BM, Chadwick LR (2005) In vitro susceptibility of Helicobacter pylori to botanical extracts used traditionally for the treatment of gastrointestinal disorders. Phytother Res 19:988–991

    Article  PubMed  Google Scholar 

  28. Parkin DM (2001) Global cancer statistics in the year 2000. Lancet Oncol 2:533–543

    Article  PubMed  CAS  Google Scholar 

  29. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  30. Pellicano R, Mazzaferro V, Grigioni WF, Cutufia MA, Fagoonee S, Silengo L, Rizzetto M, Ponzetto A (2004) Helicobacter species sequences in liver samples from patients with and without hepatocellular carcinoma. World J Gastroenterol 10:598–601

    PubMed  CAS  Google Scholar 

  31. Piantadosi S, Byar DP, Green SB (1988) The ecological fallacy. Am J Epidemiol 127:893–904

    PubMed  CAS  Google Scholar 

  32. Prieto J (2008) Inflammation, HCC and sex: IL-6 in the centre of the triangle. J Hepatol 48:380–381

    Article  PubMed  CAS  Google Scholar 

  33. Quaglia NC, Dambrosio A, Normanno G, Parisi A, Patrono R, Ranieri G, Rella A, Celano GV (2008) High occurrence of Helicobacter pylori in raw goat, sheep and cow milk inferred by glmM gene: a risk of food-borne infection? Int J Food Microbiol 124:43–47

    Article  PubMed  CAS  Google Scholar 

  34. Satoh K, Yoshida Y, Taniguchi Y, Kimura K (1993) Relationship between Helicobacter pylori colonization in the gastric mucosa and the severity of atrophic gastritis. Nihon Rinsho 51:3227–3230

    PubMed  CAS  Google Scholar 

  35. Studach LL, Menne S, Cairo S, Buendia MA, Hullinger RL, Lefrancois L, Merle P, Andrisani OM (2012) A subset of Suz12/PRC2 target genes is activated during HBV replication and liver carcinogenesis associated with hepatitis B virus X protein. Hepatology 56:1240–1251

    Article  PubMed  CAS  Google Scholar 

  36. Tan VP, Wong BC (2011) Helicobacter pylori and gastritis: untangling a complex relationship 27 years on. J Gastroenterol Hepatol 26(Suppl 1):42–45

    Article  PubMed  Google Scholar 

  37. Verhoef C, Pot RG, de Man RA, Zondervan PE, Kuipers EJ, JN IJ, Kusters JG (2003) Detection of identical Helicobacter DNA in the stomach and in the non-cirrhotic liver of patients with hepatocellular carcinoma. Eur J Gastroenterol Hepatol 15:1171–1174

    Article  PubMed  Google Scholar 

  38. Vivekanandan P, Torbenson M (2008) Low frequency of Helicobacter DNA in benign and malignant liver tissues from Baltimore, United States. Hum Pathol 39:213–216

    Article  PubMed  CAS  Google Scholar 

  39. Wang N, Zheng Y, Yu X, Lin W, Chen Y, Jiang Q (2009) Sex-modified effect of hepatitis B virus infection on mortality from primary liver cancer. Am J Epidemiol 169:990–995

    Article  PubMed  Google Scholar 

  40. Ward JM, Fox JG, Anver MR, Haines DC, George CV, Collins MJ Jr, Gorelick PL, Nagashima K, Gonda MA, Gilden RV et al (1994) Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species. J Natl Cancer Inst 86:1222–1227

    Article  PubMed  CAS  Google Scholar 

  41. Xuan SY, Li N, Qiang X, Zhou RR, Shi YX, Jiang WJ (2006) Helicobacter infection in hepatocellular carcinoma tissue. World J Gastroenterol 12:2335–2340

    PubMed  CAS  Google Scholar 

  42. Yang L (2006) Incidence and mortality of gastric cancer in China. World J Gastroenterol 12:17–20

    PubMed  Google Scholar 

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Acknowledgments

This study was supported by the start-up funds from Indiana University Simon Cancer Center (to Dr. Jianjun Zhang).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health at IUPUI, 714 N Senate Avenue, Suite EF 205, Indianapolis, IN, 46202, USA

    Ling Wang, Terrell Zollinger & Jianjun Zhang

  2. Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, OH, USA

    Ling Wang

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  1. Ling Wang
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  2. Terrell Zollinger
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  3. Jianjun Zhang
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Correspondence to Jianjun Zhang.

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Wang, L., Zollinger, T. & Zhang, J. Association between Helicobacter pylori infection and liver cancer mortality in 67 rural Chinese counties. Cancer Causes Control 24, 1331–1337 (2013). https://doi.org/10.1007/s10552-013-0211-3

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  • DOI: https://doi.org/10.1007/s10552-013-0211-3

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