Skip to main content

Advertisement

SpringerLink
Log in

Gastric Hyposecretion in Esophageal Squamous-Cell Carcinomas

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Recently, gastric fundic atrophy is reported to be an independent risk factor for esophageal squamous-cell carcinoma (ESCC). The aim of this study is to investigate the acid secretory level in ESCC in a case-control study. From April 2004 to March 2008, 100 consecutive subjects with early ESCC and 100 age- and sex-matched asymptomatic controls were prospectively enrolled. Gastrin-stimulated acid output was assessed by endoscopic gastrin test. Conditional regression analyses were used to adjust for other potential confounders. Multivariate analyses revealed a strong association between profound hypochlorhydria and ESCC with odds ratio (95% confidence interval): 6.0 (1.9–18.4). The association remained significant after adjusting for the effect of gastric atrophy as a covariate. The association became stronger as the ESCC developed more distal site of the esophagus. This study indicates that profound hypochlorhydria is a strong independent risk factor for ESCC even after adjusting for the influence of gastric atrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CI:

Confidence interval

EGT:

Endoscopic gastrin test

ESCC:

Esophageal squamous-cell carcinoma

ER:

Endoscopic resection

OR:

Odds ratio

References

  1. Lambert R, Hainaut P. Epidemiology of oesophagogastric cancer. Best Pract Res Clin Gastroenterol. 2007;21:921–945. doi:10.1016/j.bpg.2007.10.001.

    Article  CAS  PubMed  Google Scholar 

  2. Center for cancer control and information services, national cancer center, Japan. http://ganjoho.ncc.go.jp/pro/statistics/en/graph_db_index.html; 2009.

  3. Kuwano H, Morita M, Tsutsui S, Kido Y, Mori M, Sugimachi K. Comparison of characteristics of esophageal squamous cell carcinoma associated with head and neck cancer and those with gastric cancer. J Surg Oncol. 1991;46:107–109. doi:10.1002/jso.2930460208.

    Article  CAS  PubMed  Google Scholar 

  4. Kodama M, Kakegawa T. Treatment of superficial cancer of the esophagus: a summary of responses to a questionnaire on superficial cancer of the esophagus in Japan. Surgery. 1998;123:432–439.

    CAS  PubMed  Google Scholar 

  5. Kokawa A, Yamaguchi H, Tachimori Y, Kato H, Watanabe H, Nakanishi Y. Other primary cancers occurring after treatment of superficial oesophageal cancer. Br J Surg. 2001;88:439–443. doi:10.1046/j.1365-2168.2001.01696.x.

    Article  CAS  PubMed  Google Scholar 

  6. Khuroo MS, Zargar SA, Mahajan R, Banday MA. High incidence of oesophageal and gastric cancer in Kashmir in a population with special personal and dietary habits. Gut. 1992;33:11–15. doi:10.1136/gut.33.1.11.

    Article  CAS  PubMed  Google Scholar 

  7. Ye W, Held M, Lagergren J, et al. Helicobacter pylori infection and gastric atrophy: risk of adenocarcinoma and squamous-cell carcinoma of the esophagus and adenocarcinoma of the gastric cardia. J Natl Cancer Inst. 2004;96:388–396.

    Article  PubMed  Google Scholar 

  8. Ye W, Nyren O. Risk of cancers of the oesophagus and stomach by histology or subsite in patients hospitalized for pernicious anaemia. Gut. 2003;52:938–941. doi:10.1136/gut.52.7.938.

    Article  CAS  PubMed  Google Scholar 

  9. Iijima K, Koike T, Abe Y, et al. Extensive gastric atrophy: an increased risk factor for superficial esophageal squamous-cell carcinoma in Japan. Am J Gastroenterol. 2007;102:1603–1609. doi:10.1111/j.1572-0241.2007.01257.x.

    Article  PubMed  Google Scholar 

  10. Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988;48:3554–3560.

    CAS  PubMed  Google Scholar 

  11. Rohrer GV, Welsh JD. Correlative study: gastric secretion and histology. Gastroenterology. 1967;52:185–191.

    CAS  PubMed  Google Scholar 

  12. El-Omar EM, Oien K, El-Nujumi A, et al. l. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology. 1997;113:15–24. doi:10.1016/S0016-5085(97)70075-1.

    Article  CAS  PubMed  Google Scholar 

  13. Gutierrez O, Melo M, Segura AM, Angel A, Genta RM, Graham DY. Cure of Helicobacter pylori infection improves gastric acid secretion in patients with corpus gastritis. Scand J Gastroenterol. 1997;32:664–668. doi:10.3109/00365529708996515.

    Article  CAS  PubMed  Google Scholar 

  14. Takeshita K, Tani M, Inoue H, et al. Endoscopic treatment of early esophageal or gastric cancer. Gut. 1997;40:123–127.

    CAS  PubMed  Google Scholar 

  15. Makuuchi H. Endoscopic mucosal resection for early esophageal cancer: indication and techniques. Dig Endosc. 1996;8:175–179.

    Google Scholar 

  16. Inoue H, Tani M, Nagai K, et al. Treatment of esophageal and gastric tumors. Endoscopy. 1993;31:47–55. doi:10.1055/s-1999-13647.

    Article  Google Scholar 

  17. Muir CS, Mckinney PA. Cancer of the esophagus: a global overview. Eur J Cancer Prev. 1992;1:259–264. doi:10.1097/00008469-199204000-00007.

    Article  CAS  PubMed  Google Scholar 

  18. Goldstein HM, Zornoza J. Association of squamous cell carcinoma of the head and neck with cancer of the esophagus. AJR Am J Roentgenol. 1978;131:791–794.

    CAS  PubMed  Google Scholar 

  19. Misiewicz JJ, Tytgat GN, Goodwin CS. The Sydney system; a new classification of gastritis. Working party reports; 1990: 1–10.

  20. Miki K. Gastric cancer screening using the serum pepsinogen test method. Gastric Cancer. 2006;9:245–253. doi:10.1007/s10120-006-0397-0.

    Article  PubMed  Google Scholar 

  21. Yanaoka K, Oka M, Mukoubayashi C, et al. Cancer high-risk subjects by serum pepsinogen tests: outcomes after 10-years follow-up in asymptomatic middle-aged males. Cancer Epidemiol Biomarkers Prev. 2008;17:838–845. doi:10.1158/1055-9965.EPI-07-2762.

    Article  CAS  PubMed  Google Scholar 

  22. Iijima K, Ohara S, Sekine H, et al. A new endoscopic method of gastric acid secretory testing. Am J Gastroenterol. 1998;93:2113–2118. doi:10.1111/j.1572-0241.1998.00603.x.

    Article  CAS  PubMed  Google Scholar 

  23. Iijima K, Ohara S, Sekine H, et al. Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication. Gut. 2000;46:20–26. doi:10.1136/gut.46.1.20.

    Article  CAS  PubMed  Google Scholar 

  24. Koike T, Ohara S, Sekine H, et al. Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion. Gut. 2001;49:330–334. doi:10.1136/gut.49.3.330.

    Article  CAS  PubMed  Google Scholar 

  25. Iijima K, Sekine H, Koike T, Imatani A, Ohara S, Shimosegawa T. Long-term effect of Helicobacter pylori eradication on the reversibility of acid secretion in profound hypochlorhydria. Aliment Pharmacol Ther. 2004;19:1181–1188. doi:10.1111/j.1365-2036.2004.01948.x.

    Article  CAS  PubMed  Google Scholar 

  26. Gao YT, McLaughlin JK, Blot WJ, et al. Risk factors for esophageal cancer in Shanghai, China. I. Role of cigarette smoking and alcohol drinking. J Cancer. 1994;58:192–196.

    CAS  Google Scholar 

  27. Takezaki T, Shinoda M, Hatooka S, et al. Subsite-specific risk factors for hypopharyngeal and esophageal cancer (Japan). Cancer Causes Control. 2000;11:597–608. doi:10.1023/A:1008909129756.

    Article  CAS  PubMed  Google Scholar 

  28. International Agency for Research on Cancer. Alcohol drinking. IARC Monogr. 1988;44:186–194.

    Google Scholar 

  29. International Agency for Research on Cancer. Tobacco smoking. IARC Monogr. 1986;38:270–275.

    Google Scholar 

  30. Segawa K, Nakazawa S, Tsukamoto Y, et al. Chronic alcohol abuse leads to gastric atrophy and decreased gastric secretory capacity: a histological and physiological study. Am J Gastroenterol. 1988;83:373–379.

    CAS  PubMed  Google Scholar 

  31. Whitfield PF, Hobsley M. Comparison of maximal gastric secretion in smokers and non-smokers with and without duodenal ulcer. Gut. 1987;28:557–560. doi:10.1136/gut.28.5.557.

    Article  CAS  PubMed  Google Scholar 

  32. Iijima K, Ohara S, Koike T, Sekine H, Shimosegawa T. Gastric acid secretion of normal Japanese subjects in relation to Helicobacter pylori infection, aging, and gender. Scand J Gastroenterol. 2004;39:709–716. doi:10.1080/00365520410005911.

    Article  CAS  PubMed  Google Scholar 

  33. Haruma K, Komoto K, Kawaguchi H, et al. Pernicious anemia and Helicobacter pylori infection in Japan: evaluation in a country with a high prevalence of infection. Am J Gastroenterol. 1995;90:1107–1110.

    CAS  PubMed  Google Scholar 

  34. El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1 polymorphism associated with increased risk of gastric cancer. Nature. 2000;404:398–402. (correction published in Nature 2001;412:99).

    Article  CAS  PubMed  Google Scholar 

  35. Ohyauchi M, Imatani A, Yonechi M, et al. The polymorphism interleukin 8–251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut. 2005;54:330–335. doi:10.1136/gut.2003.033050.

    Article  CAS  PubMed  Google Scholar 

  36. Svendsen JH, Svendsen CD, Christiansen PM. Gastric cancer risk in achlorhydric patients. A long-term follow-up study. Scand J Gastroenterol. 1986;21:16–20. doi:10.3109/00365528609034615.

    Article  CAS  PubMed  Google Scholar 

  37. Mowat C, William C, Gillen D, et al. Omeprazole, Helicobacter pylori status and alteration in the intragastric milieu facilitating bacterial N-nitrosation. Gastroenterology. 2000;119:339–347. doi:10.1053/gast.2000.9367.

    Article  CAS  PubMed  Google Scholar 

  38. Mirvish SS. Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. Cancer Lett. 1995;29:17–48. doi:10.1016/0304-3835(95)03786-V.

    Article  Google Scholar 

  39. Väkeväinen S, Mentula S, Nuutinen H, et al. Ethanol-derived microbial production of carcinogenic acetaldehyde in achlorhydric atrophic gastritis. Scand J Gastroenterol. 2002;37:648–655. doi:10.1080/00365520212500.

    Article  PubMed  Google Scholar 

  40. Väkeväinen S, Tillonen J, Salaspuro M, Jousimies-Somer H, Nuutinen H, Färkkilä M. Hypochlorhydria induced by a proton pump inhibitor leads to intragastric microbial production of acetaldehyde from ethanol. Aliment Pharmacol Ther. 2000;14:1511–1518. doi:10.1046/j.1365-2036.2000.00858.x.

    Article  PubMed  Google Scholar 

  41. Vaca CE, Nilsson JA, Fang JL, Grafström RC. Formation of DNA adducts in human buccal epithelial cells exposed to acetaldehyde and methylglyoxal in vivo. Chem Biol Interact. 1998;108:197–208. doi:10.1016/S0009-2797(97)00107-5.

    Article  CAS  PubMed  Google Scholar 

  42. Murphy SJ, Anderson LA, Johnston BT, et al. Have patients with esophagitis got an increased risk of adenocarcinoma? Results from a population-based study. World J Gastroenterol. 2005;11:7290–7295.

    PubMed  Google Scholar 

  43. McColl KE. Helicobacter pylori and oesophageal cancer–not always protective. Gut. 2007;56:457–459. doi:10.1136/gut.2006.111385.

    Article  CAS  PubMed  Google Scholar 

  44. Grossman MI, Kirsner JB, Gillespie IE. Basal and histalog-stimulated gastric secretion in control subjects and in patients with peptic ulcer or gastric cancer. Gastoenterology. 1963;45:14–26.

    CAS  Google Scholar 

  45. Inomata Y, Koike T, Ohara S, et al. Preservation of gastric acid secretion may be important for the development of gastro-esophageal junction adenocarcinoma in Japanese people, irrespective of the H. pylori infection status. Am J Gastroenterol. 2006;101:926–933. doi:10.1111/j.1572-0241.2006.00497.x.

    Article  PubMed  Google Scholar 

  46. Abe Y, Ohara S, Koike T, et al. The prevalence of Helicobacter pylori infection and the status of gastric acid secretion in patients with Barrett’s esophagus in Japan. Am J Gastroenterol. 2004;99:1213–1221. doi:10.1111/j.1572-0241.2004.30313.x.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan

    K. Iijima, T. Koike, Y. Abe, H. Yamagishi, N. Ara, K. Asanuma, K. Uno, A. Imatani, S. Ohara & T. Shimosegawa

  2. Division of Epidemiology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

    N. Nakaya

Authors
  1. K. Iijima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y. Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Yamagishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. Ara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Asanuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. Uno
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. Imatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N. Nakaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S. Ohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T. Shimosegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Iijima.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iijima, K., Koike, T., Abe, Y. et al. Gastric Hyposecretion in Esophageal Squamous-Cell Carcinomas. Dig Dis Sci 55, 1349–1355 (2010). https://doi.org/10.1007/s10620-009-0853-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-009-0853-x

Keywords

Search

Navigation