Abstract
Multiple cancers frequently occur in the upper aerodigestive tract. The high incidence rate of multiple carcinomas in this region is often explained in terms of involvement of the same underlying risk factors. It has been reported that the oral bacterium Streptococcus anginosus (S. anginosus) is associated with esophageal, gastric, and pharyngeal cancer tissues. In this study, a highly specific quantification method for S. anginosus DNA using real‐time PCR was established. We employed this assay to determine whether S. anginosus is also associated with oral cancer tissues. This precise quantification method revealed different degrees of infection with S. anginosus in esophageal cancer and oral cancer. We assayed 10 ng of genomic DNA from cancer tissues, and found that eight of 18 samples (44%) from the esophagus contained a detectable level (>10 fg) of S. anginosus DNA, whereas this was the case for only five of 38 samples (13%) of oral cancer. The quantity of S. anginosus DNA in the esophageal cancer tissues was significantly higher than in oral cancer. The maximum amount of S. anginosus DNA was approximately ten times higher in esophageal than in oral cancer tissues. In addition, none of the five different oral cancer sites (floor of the mouth, mandibular gingival, maxillary gingival, buccal mucosal, and tongue) showed significant signs of S. anginosus infection. On the other hand, most non‐cancerous tissues of the esophagus and tongue showed an undetectable level of S. anginosus. These results suggest that S. anginosus is associated with esophageal cancer, but is not closely related with oral cancer.
References
- 1. Katoh M, Terada M. Oncogene and tumor suppressor genes. In: Nishi M, Ichikawa H, Nakajima T, Maruyama K, Tahara E, editors. Gastric cancer. Tokyo : Springer‐Verlag; 1993. p. 196–208. [Google Scholar]
- 2. Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez‐Perez GI, Blaser MJN. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. Engl J Med 1991; 325: 1132–6. [DOI] [PubMed] [Google Scholar]
- 3. Fukuda H, Saito D, Hayashi S, Hisai H, Ono H, Yoshida S, Oguro Y, Noda T, Sato T, Katoh M, Terada M, Sugimura T. Helicobacter pylori infection, serum pepsinogen level and gastric cancer: a case‐control study in Japan. Jpn J Cancer Res 1995; 86: 64–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Honda S, Fujioka T, Tokieda M, Satoh R, Nishizono A, Nasu M. Development of H. pylori‐induced gastric carcinoma in Mongolian gerbils. Cancer Res 1998; 58: 4255–9. [PubMed] [Google Scholar]
- 5. Sasaki H, Igaki H, Ishizuka T, Kogoma Y, Sugimura T, Terada M. Presence of Streptococcus DNA sequence in surgical specimens of gastric cancer. Jpn J Cancer Res 1995; 86: 791–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Sasaki H, Ishizuka T, Muto M, Nezu M, Nakanishi Y, Inagaki Y, Watanabe H, Watanabe H, Terada M. Presence of Streptococcus anginosus DNA in esophageal cancer, dysplasia of esophageal, and gastric cancer. Cancer Res 1998; 58: 2991–5. [PubMed] [Google Scholar]
- 7. Piscitelli SC, Shwed J, Schreckenberger P, Danziger LH. Streptococcus mil‐leri group: renewed interest in an elusive pathogen. Eur J Clin Microbiol Infect Dis 1992; 11:491–8. [DOI] [PubMed] [Google Scholar]
- 8. Whiley RA, Fraser HY, Hardie JM, Beighton D. Phenotypic differentiation of Streptococcus intermedius, Streptococcus constettatus, and Streptococcus anginosus strains within the “Streptococcus milleri group”. J Clin Microbiol 1990; 28: 1497–511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Whiley RA, Beighton D, Winstanley TG, Fraser HY, Hardie JM. Streptococcus intemedius, Streptococcus constettatus, and Streptococcus anginosus (the Streptococcus milleri group): association with different body sites and clinical infections. J Clin Microbiol 1992; 30: 243–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Tateda M, Shiga K, Saijo S, Sone M, Hori T, Yokoyama J, Matsuura K, Takasaka T. Streptococcus anginosus in head and neck squamous cell carcinoma: implication in carcinogenesis. Int J Mol Med 2000; 6: 699–703. [DOI] [PubMed] [Google Scholar]
- 11. Berg JW, Schottenfeld D, Ritter F. Incidence of multiple primary cancers. III. Cancers of the respiratory and upper digestive system as multiple primary cancers. J Natl Cancer Inst 1970; 44: 263–74. [PubMed] [Google Scholar]
- 12. Donald PV, Danville P. Multiple primary malignancies of the upper aerodi‐gestive system. Ann Otol 1979; 88: 846–54. [DOI] [PubMed] [Google Scholar]
- 13. Kato I, Nomura AMY. Alcohol in the aetiology of upper aerodigestive tract cancer. Oral Oncol Eur J Cancer 1994; 30B: 75–81. [DOI] [PubMed] [Google Scholar]
- 14. Franceschi S, Gloghini A, Maestro R, Barzan L, Bidoli R, Talamini T, Vukosalvljevic T, Carbone A, Boiocchi M. Analysis of the p53 gene in relation to tobacco and alcohol in cancers of the upper aero‐digestive tract. Int J Cancer 1995; 60: 872–6. [DOI] [PubMed] [Google Scholar]
- 15. Whiley RA, Beighton D. Current classification of the oral Streptococci . Oral Microbiol Immunol 1998; 13: 195–216. [DOI] [PubMed] [Google Scholar]
- 16. Flynn CE, Ruoff KL. Identification of “Streptococcus milleri” group isolates to the species level with a commercially available rapid test system. J Clin Microbiol 1995; 33: 2704–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Chen W, Martinez G, Mulchandani A. Molecular beacons: a real‐time poly‐merase chain reaction assay for detecting Salmonella . Anal Biochem 2000; 280: 166–72. [DOI] [PubMed] [Google Scholar]
- 18. Wheeler DL, Chappey C, Lash AE, Leipe DD, Madden TL, Schuler GD, Tatusova TA, Rapp BA. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 2000; 28: 10–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position‐specific gap penalties and weight matrix choice. Nucleic Acids Res 1994; 22: 4673–80. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Jacobs JA, Schot CS, Schouls LM. The Streptococcus anginosus species comprises five 16S rRNA ribogroups with different phenotypic characteristics and clinical relevance. Int J Syst Evol Microbiol 2000; 50: 1073–79. [DOI] [PubMed] [Google Scholar]