Association between Helicobacter pylori Infection and Pancreatic Cancer. A Cumulative Meta-Analysis
Context Infection with Helicobacter pylori (H. pylori) has been implicated in the etiopathogenesis of various malignant conditions. Notwithstanding, its etiological association with pancreatic cancer remains inconclusive. Studies focusing on the relationship between H. pylori infection and pancreatic cancer risk have yielded conflicting results. Objective The aim of this study was to obtain a reliable estimate of the risk of H. pylori infection in causing pancreatic cancer, by performing a meta-analysis of the existing observational studies evaluating the association. Methods/Statistics Observational studies comparing the prevalence of H. pylori infection in patients with pancreatic cancer and healthy controls, conducted in adult populations and published in all languages, were identified through systematic search in the MEDLINE and EMBASE up to April 2010. H. pylori infection was confirmed by serological testing using an antigen-specific enzyme-linked immunosorbent assay. Pooled adjusted odds ratios (AOR) and associated 95% confidence intervals (CI) were obtained by using a DerSimonian and Laird random-effects model. Results Six studies involving a total of 2,335 patients met our eligibility criteria. A significant association between H. pylori seropositivity and development of pancreatic cancer (AOR 1.38, 95% CI: 1.08-1.75; P=0.009) was seen. No significant association was seen on pooled analysis of the three studies assessing the relationship between cytotoxin-associated gene A (CagA) positivity and pancreatic cancer. A cumulative meta-analysis suggested a reducing, albeit statistically significant association as the evidence was accumulated. Conclusions The pooled data suggests an association between infection with H. pylori and the development of pancreatic cancer. Further research is needed to confirm our findings.
Image: Forest plot of the association between H. pylori and pancreatic cancer.
American Cancer Society. Cancer facts and figures 2004. Atlanta, GA, USA: American Cancer Society, 2004.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009; 59:225-49. [PMID 19474385]
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004; 363:1049-57. [PMID 15051286]
Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol 2009; 6:699-708. [PMID 19806144]
Marshall BJ. Helicobacter pylori. Am J Gastroenterol 1994; 89(8 Suppl):S116-28. [PMID 8048402]
Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology 2007; 133:659-72. [PMID 17681184]
Raderer M, Wrba F, Kornek G, Maca T, Koller DY, Weinlaender G, et al. Association between Helicobacter pylori infection and pancreatic cancer. Oncology 1998; 55:16-9. [PMID 9428370]
Stolzenberg-Solomon RZ, Blaser MJ, Limburg PJ, Perez-Perez G, Taylor PR, Virtamo J, et al. Helicobacter pylori seropositivity as a risk factor for pancreatic cancer. J Natl Cancer Inst 2001; 93:937-41. [PMID 11416115]
Lindkvist B, Johansen D, Borgström A, Manjer J. A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer. BMC Cancer 2008; 8:321. [PMID 18986545]
de Martel C, Llosa AE, Friedman GD, Vogelman JH, Orentreich N, Stolzenberg-Solomon RZ, Parsonnet J. Helicobacter pylori infection and development of pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2008; 17:1188-94. [PMID 18483341]
Risch HA, Yu H, Lu L, Kidd MS. ABO blood group, Helicobacter pylori seropositivity, and risk of pancreatic cancer: A case-control study. J Natl Cancer Inst 2010; 102:502-5. [PMID 20181960]
Wadstrom T, Fryzek JP, Demirjian S, Choi JW, Garabrant DH, Nyren O, et al. Antibodies to Helicobacter bills in patients with pancreatic carcinoma. Helicobacter 2004; 9:538.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283:2008-12. [PMID 10789670]
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7:177-88. [PMID 3802833]
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327:557-60. [PMID 12958120]
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315:629-34. [PMID 9310563]
Zagari RM, Bazzoli F. Gastric cancer: who is at risk? Dig Dis 2004; 22:302-5. [PMID 15812151]
Blaser MJ, Nomura A, Lee J, Stemmerman GH, Perez-Perez GI. Early-life family tructure and microbially induced cancer risk. PLoS Med 2007; 4:e7. [PMID 17227131]
Dasanu CA, Rathmann J, Alexandrescu DT. H. pylori-associated gastric cancer in a husband-wife pair: a veritable family affair. South Med J 2009; 102:1158-60. [PMID 19864985]
Kosunen TY, Pukkala E, Seppala K, Tilvis R, Sipponen P, Aromaa A, et al. The effect of eradication therapy for Helicobacter infection on the incidence of gastric and other cancers. Helicobacter 2004; 9:534.
Zhao Y, Wang F, Chang D, Han B, You DY. Meta-analysis of different test indicators: Helicobacter pylori infection and the risk of colorectal cancer. Int J Colorectal Dis 2008; 23:875-82. [PMID 18506454]
Xuan S, Xin Y, Chen A, Dong QJ, Qiang X, Lin N, et al. Association between the presence of H pylori in the liver and hepatocellular carcinoma: a meta-analysis. World J Gastroenterol 2008; 14:307-312. [PMID 18186573]
Zhuo WL, Zhu B, Xiang ZL, Zhuo XL, Cai L, Chen ZT. Assessment of the relationship between Helicobacter pylori and lung cancer: a meta-analysis. Arch Med Res 2009; 40:406-10. [PMID 19766906]
Zhuo XL, Wang Y, Zhuo WL, Zhang XY. Possible association of Helicobacter pylori infection with laryngeal cancer risk: an evidence-based meta-analysis. Arch Med Res 2008; 39:625-8. [PMID 18662596]
Zhuo X, Zhang Y, Wang Y, Zhuo W, Zhu Y, Zhang X. Helicobacter pylori infection and oesophageal cancer risk: association studies via evidence-based meta-analyses. Clin Oncol (R Coll Radiol) 2008; 20:757-62. [PMID 18793831]
Nilsson H, Stenram U, Ihse I, Wadstrom T. Helicobacter species ribosomal DNA in the pancreas, stomach and duodenum of pancreatic cancer patients. World J Gastroenterol 2006; 12:3038-43. [PMID 16718784]
Takayama S, Takahashi H, Matsuo Y, Okada Y, Manabe T. Effects of Helicobacter pylori infection on human pancreatic cancer cell line. Hepatogastroenterology 2007; 54:2387-91. [PMID 18265671]
Aihara M, Tsuchimoto D, Takizawa H, Azuma A, Wakebe H, Ohmoto Y, et al. Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. Infect Immun 1997; 65:3218-24. [PMID 9234778]
Seo JH, Lim JW, Kim H, Kim KH. Helicobacter pylori in a Korean isolate activates mitogen-activated protein kinases, AP-1, and NF-kappaB and induces chemokine expression in gastric epithelial AGS cells. Lab Invest 2004; 84:49-62. [PMID 14631383]
Risch HA. Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity. J Natl Cancer Inst 2003; 95:948-60. [PMID 12837831]
Howatson AG, Carter DC. Pancreatic carcinogenesis: effect of secretin in the hamster- nitrosamine model. J Natl Cancer Inst 1987; 78:101-5. [PMID 3467121]
Hsing AW, Hansson LE, McLaughlin JK, Nyren O, Blot WJ, Ekbom A, et al. Pernicious anemia and subsequent cancer. A population-based cohort study. Cancer 1993; 71:745-50. [PMID 8431855]
Annibale B, Capurso G, Delle Fave G. Consequences of Helicobacter pylori infection on the absorption of micronutrients. Dig Liver Dis 2002; 34(Suppl 2):S72-77. [PMID 12408446]
Luo J, Nordenvall C, Nyrén O, Adami HO, Permert J, Ye W. The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer 2007; 120:368-72. [PMID 17044024]
Copyright (c) 2011 Guru Trikudanathan, Aby Philip, Constantin A Dasanu, William L Baker
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