All Title Author
Keywords Abstract

PLOS ONE  2013 

Association between Selected Oral Pathogens and Gastric Precancerous Lesions

DOI: 10.1371/journal.pone.0051604

Full-Text   Cite this paper   Add to My Lib


We examined whether colonization of selected oral pathogens is associated with gastric precancerous lesions in a cross-sectional study. A total of 119 participants were included, of which 37 were cases of chronic atrophic gastritis, intestinal metaplasia, or dysplasia. An oral examination was performed to measure periodontal indices. Plaque and saliva samples were tested with real-time quantitative PCR for DNA levels of pathogens related to periodontal disease (Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Actinobacillus actinomycetemcomitans) and dental caries (Streptococcus mutans and S. sobrinus). There were no consistent associations between DNA levels of selected bacterial species and gastric precancerous lesions, although an elevated but non-significant odds ratio (OR) for gastric precancerous lesions was observed in relation to increasing colonization of A. actinomycetemcomitans (OR = 1.36 for one standard deviation increase, 95% Confidence Interval = 0.87–2.12), P. gingivalis (OR = 1.12, 0.67–1.88) and T. denticola (OR = 1.34, 0.83–2.12) measured in plaque. To assess the influence of specific long-term infection, stratified analyses by levels of periodontal indices were conducted. A. actinomycetemcomitans was significantly associated with gastric precancerous lesions (OR = 2.51, 1.13–5.56) among those with ≥ median of percent tooth sites with PD≥3 mm, compared with no association among those below the median (OR = 0.86, 0.43–1.72). A significantly stronger relationship was observed between the cumulative bacterial burden score of periodontal disease-related pathogens and gastric precancerous lesions among those with higher versus lower levels of periodontal disease indices (p-values for interactions: 0.03–0.06). Among individuals with periodontal disease, high levels of colonization of periodontal pathogens are associated with an increased risk of gastric precancerous lesions.


[1]  Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127: 2893–2917.
[2]  Terry MB, Gaudet MM, Gammon MD (2002) The epidemiology of gastric cancer. Semin Radiat Oncol 12: 111–127.
[3]  Crew KD, Neugut AI (2006) Epidemiology of gastric cancer. World J Gastroenterol 12: 354–362.
[4]  Correa P, Piazuelo MB, Camargo MC (2004) The future of gastric cancer prevention. Gastric Cancer 7: 9–16.
[5]  Engel LS, Chow WH, Vaughan TL, Gammon MD, Risch HA, et al. (2003) Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst 95: 1404–13.
[6]  Lauren P (1965) The two histological main types of gastric carcinoma: diffise and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 64: 31–49.
[7]  Correa P (1988) A human model of gastric carcinogenesis. Cancer Res 48: 3554–3560.
[8]  Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M (1975) A model for gastric cancer epidemiology. Lancet 2: 58–60.
[9]  Fontham ET, Ruiz B, Perez A, Hunter F, Correa P (1995) Determinants of Helicobacter pylori infection and chronic gastritis. Am J Gastroenterol 90: 1094–1101.
[10]  Fontham E, Zavala D, Correa P, Rodriguez E, Hunter F, et al. (1986) Diet and chronic atrophic gastritis: a case-control study. J Natl Cancer Inst 76: 621–627.
[11]  Farinati F, Cardin R, Libera GD, Rugge M, Herszènyi L, et al. (1995) Determinants for the development of chronic atrophic gastritis and intestinal metaplasia in the stomach. Eur J Cancer Prev 4: 181–186.
[12]  Kato I, Vivas J, Plummer M, Lopez G, Peraza S, et al. (2004) Environmental factors in Helicobacter pylori-related gastric precancerous lesions in Venezuela. Cancer Epidemiol Biomarkers Prev 13: 468–476.
[13]  Weck MN, Brenner H (2006) Prevalence of chronic atrophic gastritis in different parts of the world. Cancer Epidemiol Biomarkers Prev 15: 1083–1094.
[14]  Peleteiro B, Lunet N, Figueiredo C, Carneiro F, David L, et al. (2007) Smoking, Helicobacter pylori virulence, and type of intestinal metaplasia in Portuguese males. Cancer Epidemiol Biomarkers Prev 16: 322–326.
[15]  Abnet CC, Kamangar F, Dawsey SM, Stolzenberg-Solomon RZ, Albanes D, et al. (2005) Tooth loss is associated with increased risk of gastric non-cardia adenocarcinoma in a cohort of Finnish smokers. Scand J Gastroenterol 40: 681–687.
[16]  Abnet CC, Qiao YL, Mark SD, Dong ZW, Taylor PR, et al. (2001) Prospective study of tooth loss and incident esophageal and gastric cancers in China. Cancer Causes Control 12: 847–854.
[17]  Watabe K, Nishi M, Miyake H, Hirata K (1998) Lifestyle and gastric cancer: a case-control study. Oncol Rep 5: 1191–1194.
[18]  Demirer T, Icli F, Uzunalimoglu O, Kucuk O (1990) Diet and stomach cancer incidence. A case-control study in Turkey. Cancer 65: 2344–2348.
[19]  Michaud DS, Liu Y, Meyer M, Giovannucci E, Joshipura K (2008) Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study. Lancet Oncol 9: 550–558.
[20]  Salazar CR, Francois F, Li Y, Corby P, Hays R, et al. (2012) Association between oral health and gastric precancerous lesions. Carcinogenesis 33: 399–403.
[21]  Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr (1998) Microbial complexes in subgingival plaque. J Clin Periodontol 25: 134–144.
[22]  Kigure T, Saito A, Seida K, Yamada S, Ishihara K, et al. (1995) Distribution of Porphyromonas gingivalis and Treponema denticola in human subgingival plaque at different periodontal pocket depths examined by immunohistochemical methods. J Periodontal Res 30: 332–341.
[23]  Buchmann R, Muller RF, Heinecke A, Lange DE (2000) Actinobacillus actinomycetemcomitans in destructive periodontal disease. Three-year follow-up results. J Periodontol 71: 444–453.
[24]  Slots J, Ting M (1999) Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontol 2000 20: 82–121.
[25]  Hamada S, Slade HD (1980) Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev 44: 331–384.
[26]  Whiley RA, Beighton D (1998) Current classification of the oral streptococci. Oral Microbiol Immunol 13: 195–216.
[27]  Perez-Perez GI, Dworkin BM, Chodos JE, Blaser MJ (1988) Campylobacter pylori antibodies in humans. Ann Intern Med 109: 11–17.
[28]  Blaser MJ, Perez-Perez GI, Kleanthous H, Cover TL, Peek RM, et al. (1995) Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55: 2111–2115.
[29]  Francois F, Roper J, Goodman AJ, Pei Z, Ghumman M, et al. (2008) The association of gastric leptin with oesophageal inflammation and metaplasia. Gut 57: 16–24.
[30]  Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 20: 1161–1181.
[31]  National Institute of Dental Research (1987) Epidemiology and Oral Disease Prevention Program. Oral health of United States adults: the National Survey of Oral Health in U.S. Employed Adults and Seniors, 1985–1986: national findings. Bethesda, Md.: U.S. Dept. of Health and Human Services, Public Service, National Institutes of Health.
[32]  Loe H (1967) The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol 38: Suppl: 610–616.
[33]  Li Y, Saxena D, Barnes VM, Trivedi HM, Ge Y, et al. (2006) Polymerase chain reaction-based denaturing gradient gel electrophoresis in the evaluation of oral microbiota. Oral Microbiol Immunol 21: 333–339.
[34]  Psoter WJ, Ge Y, Russell SL, Chen Z, Katz RV, et al. (2011) PCR detection of Streptococcus mutans and Aggregatibacter actinomycetemcomitans in dental plaque samples from Haitian adolescents. Clin Oral Investig 15: 461–469.
[35]  Yano A, Kaneko N, Ida H, Yamaguchi T, Hanada N (2002) Real-time PCR for quantification of Streptococcus mutans. FEMS Microbiol Lett 217: 23–30.
[36]  Breslow N, Day NE (1980) Statistical Methods in Cancer Research, Vol 1—The Analysis of Case-Control Studies. In. WHO Lyon: IARC Scientific Publication No. 32: 227–38.
[37]  Consensus report (1996) Periodontal diseases: pathogenesis and microbial factors. Ann Periodontol 1: 926–932.
[38]  Loesche WJ (1986) Role of Streptococcus mutans in human dental decay. Microbiol Rev 50: 353–380.
[39]  Kuper H, Adami HO, Trichopoulos D (2000) Infections as a major preventable cause of human cancer. J Intern Med 248: 171–183.
[40]  Pritchard DM, Crabtree JE (2006) Helicobacter pylori and gastric cancer. Curr Opin Gastroenterol 22: 620–625.
[41]  Talley NJ, Zinsmeister AR, Weaver A, DiMagno EP, Carpenter HA, et al. (1991) Gastric adenocarcinoma and Helicobacter pylori infection. J Natl Cancer Inst 83: 1734–1739.
[42]  Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, et al. (1991) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325: 1127–1131.
[43]  Fives-Taylor PM, Meyer DH, Mintz KP, Brissette C (1999) Virulence factors of Actinobacillus actinomycetemcomitans. Periodontol 2000 20: 136–167.
[44]  Zadeh HH, Nichols FC, Miyasaki KT (1999) The role of the cell-mediated immune response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in periodontitis. Periodontol 2000 20: 239–288.
[45]  Dye BA, Choudhary K, Shea S, Papapanou PN (2005) Serum antibodies to periodontal pathogens and markers of systemic inflammation. J Clin Periodontol 32: 1189–1199.
[46]  Nibali L, Ready DR, Parkar M, Brett PM, Wilson M, et al. (2007) Gene polymorphisms and the prevalence of key periodontal pathogens. J Dent Res 86: 416–420.
[47]  Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366: 1809–1820.
[48]  Casarin RC, Ribeiro Edel P, Mariano FS, Nociti FH Jr, Casati MZ, et al. (2010) Levels of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, inflammatory cytokines and species-specific immunoglobulin G in generalized aggressive and chronic periodontitis. J Periodontal Res 45: 635–642.
[49]  da Silva-Boghossian CM, do Souto RM, Luiz RR, Colombo AP (2011) Association of red complex, A. actinomycetemcomitans and non-oral bacteria with periodontal diseases. Arch Oral Biol 56: 899–906.
[50]  Blaser MJ (2010) Harnessing the power of the human microbiome. Proc Natl Acad Sci U S A 107: 6125–6126.
[51]  Foxman B, Goldberg D, Murdock C, Xi C, Gilsdorf JR (2008) Conceptualizing human microbiota: from multicelled organ to ecological community. Interdiscip Perspect Infect Dis 2008: 1–5.
[52]  Benjamini Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B (Methodological) 57: 289–300.


comments powered by Disqus