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Gastric and duodenal ulcers, periodontal disease, and risk of bladder cancer in the Health Professionals Follow-up Study

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Abstract

Purpose

Studies suggest that peptic ulcer and periodontal disease are positively associated with bladder cancer risk. These two factors are likely to share common biologic mechanisms such as inflammation and dysbiosis. We examined the joint association of peptic ulcer (gastric/duodenal) and periodontal disease on bladder cancer risk.

Methods

We conducted a prospective analysis among 45,185 men (563 invasive bladder cancer cases) in the Health Professionals Follow-Up Study (follow-up 1986–2016). History of ulcer and periodontal disease was self-reported at baseline and updated during the follow-up. Cox proportional hazards models estimated hazard ratio (HR) and 95% confidence interval (CI) for the joint associations of ulcers (gastric, duodenal) and periodontal disease, adjusting for age and other potential confounders. We tested for interaction using the Wald test for product terms.

Results

Compared with men having no history of ulcer and periodontal disease, men with a history of peptic ulcer only (HR 1.22, 95% CI 0.90–1.66) and men with a history of periodontal disease only (HR 1.19, 95% CI 0.98–1.46) were associated with higher risk of invasive bladder cancer. The highest bladder cancer risk was observed in men with a history of both peptic ulcer and periodontal disease (HR 1.52, 95% CI 1.05–2.20). Similar results were found when we stratified by ulcer types. The interactions between ulcer and periodontal disease were not statistically significant for all ulcer types (p-interaction ≥ 0.59).

Conclusion

We did not find sufficient evidence for interaction between gastric/duodenal ulcers and periodontal disease on bladder cancer risk.

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Data availability

Further information including the procedures to obtain and access data from the Health Professionals Follow-up Study is described at https://www.nurseshealthstudy.org/researchers (email: nhsaccess@channing.harvard.edu) and https://sites.sph.harvard.edu/hpfs/for-collaborators.

References

  1. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34

    PubMed  Google Scholar 

  2. Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC (2011) Association between smoking and risk of bladder cancer among men and women. JAMA 306:737–745

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Humans I, IARC Working Group (2004) Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum 83:1–1438

    Google Scholar 

  4. Pelucchi C, Negri E, Talamini R, Franceschi S, La Vecchia C (2005) Gastric and duodenal ulcer and risk of bladder cancer. Cancer Epidemiol Biomark Prev 14:550

    Google Scholar 

  5. Michaud DS, Mysliwiec PA, Aldoori W, Willett WC, Giovannucci E (2004) Peptic ulcer disease and the risk of bladder cancer in a prospective study of male health professionals. Cancer Epidemiol Biomark Prev 13:250–254

    Google Scholar 

  6. 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

    PubMed  PubMed Central  Google Scholar 

  7. Nwizu NN, Marshall JR, Moysich K et al (2017) Periodontal Disease and Incident Cancer Risk among Postmenopausal Women: Results from the Women's Health Initiative Observational Cohort. Cancer Epidemiol Biomark Prev 26:1255–1265

    Google Scholar 

  8. Arora M, Weuve J, Fall K, Pedersen NL, Mucci LA (2010) An exploration of shared genetic risk factors between periodontal disease and cancers: a prospective co-twin study. Am J Epidemiol 171:253–259

    PubMed  Google Scholar 

  9. Michaud DS, Kelsey KT, Papathanasiou E, Genco CA, Giovannucci E (2016) Periodontal disease and risk of all cancers among male never smokers: an updated analysis of the Health Professionals Follow-up Study. Ann Oncol 27:941–947

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Bryan GT (1977) The pathogenesis of experimental bladder cancer. Cancer Res 37:2813–2816

    CAS  PubMed  Google Scholar 

  11. Vermeer IT, Engels LG, Pachen DM, Dallinga JW, Kleinjans JC, van Maanen JM (2001) Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole. Gastroenterology 121:517–525

    CAS  PubMed  Google Scholar 

  12. Farinati F, Lima V, Naccarato R, Garro AJ (1989) Mutagenic activity in gastric juice and urine of subjects with chronic atrophic gastritis, gastric epithelial dysplasia and gastric cancer. Cancer Lett 48:169–175

    CAS  PubMed  Google Scholar 

  13. Nair S, Norkus EP, Hertan H, Pitchumoni CS (2000) Micronutrient antioxidants in gastric mucosa and serum in patients with gastritis and gastric ulcer: does Helicobacter pylori infection affect the mucosal levels? J Clin Gastroenterol 30:381–385

    CAS  PubMed  Google Scholar 

  14. Jaskiewicz K, Van Helden PD, Wiid IJ, Steenkamp HJ, Van Wyk MJ (1990) Chronic atrophic gastritis, gastric pH, nitrites and micronutrient levels in a population at risk for gastric carcinoma. Anticancer Res 10:833–836

    CAS  PubMed  Google Scholar 

  15. Joshipura KJ, Hung HC, Rimm EB, Willett WC, Ascherio A (2003) Periodontal disease, tooth loss, and incidence of ischemic stroke. Stroke 34:47–52

    PubMed  Google Scholar 

  16. Michaud DS, Joshipura K, Giovannucci E, Fuchs CS (2007) A prospective study of periodontal disease and pancreatic cancer in US male health professionals. J Natl Cancer Inst 99:171–175

    PubMed  Google Scholar 

  17. Si Y, Fan H, Song Y, Zhou X, Zhang J, Wang Z (2012) Association between periodontitis and chronic obstructive pulmonary disease in a Chinese population. J Periodontol 83:1288–1296

    PubMed  Google Scholar 

  18. Hung HC, Joshipura KJ, Colditz G et al (2004) The association between tooth loss and coronary heart disease in men and women. J Public Health Dent 64:209–215

    PubMed  Google Scholar 

  19. Ide R, Hoshuyama T, Wilson D, Takahashi K, Higashi T (2011) Periodontal disease and incident diabetes: a seven-year study. J Dent Res 90:41–46

    CAS  PubMed  Google Scholar 

  20. Abnet CC, Kamangar F, Dawsey SM 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

    PubMed  Google Scholar 

  21. Hajishengallis G, Sahingur SE (2014) Novel inflammatory pathways in periodontitis. Adv Dent Res 26:23–29

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ajwani S, Mattila KJ, Narhi TO, Tilvis RS, Ainamo A (2003) Oral health status, C-reactive protein and mortality–a 10 year follow-up study. Gerodontology 20:32–40

    CAS  PubMed  Google Scholar 

  23. Ebersole JL, Machen RL, Steffen MJ, Willmann DE (1997) Systemic acute-phase reactants, C-reactive protein and haptoglobin, in adult periodontitis. Clin Exp Immunol 107:347–352

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Hayashi C, Gudino CV, Gibson FC 3rd, Genco CA (2010) Review: Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways. Mol Oral Microbiol 25:305–316

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Blasco-Baque V, Garidou L, Pomie C et al (2017) Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response. Gut 66:872–885

    CAS  PubMed  Google Scholar 

  26. Kostic AD, Chun E, Robertson L et al (2013) Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14:207–215

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Schmidt J, Jentsch H, Stingu CS, Sack U (2014) General immune status and oral microbiology in patients with different forms of periodontitis and healthy control subjects. PLoS ONE 9:e109187

    PubMed  PubMed Central  Google Scholar 

  28. Cifcibasi E, Ciblak M, Kiran B et al (2015) The role of activated cytotoxic T cells in etiopathogenesis of periodontal disease: does it harm or does it heal? Sci Rep 5:9262

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim J, Amar S (2006) Periodontal disease and systemic conditions: a bidirectional relationship. Odontology 94:10–21

    PubMed  PubMed Central  Google Scholar 

  30. Hajishengallis G, Lamont RJ (2012) Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol 27:409–419

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Castellarin M, Warren RL, Freeman JD et al (2012) Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22:299–306

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Martins MD, Jiao Y, Larsson L et al (2016) Epigenetic modifications of histones in periodontal disease. J Dent Res 95:215–222

    CAS  PubMed  Google Scholar 

  33. Boylan MR, Khalili H, Huang ES et al (2014) A prospective study of periodontal disease and risk of gastric and duodenal ulcer in male health professionals. Clin Transl Gastroenterol 5:e49

    PubMed  PubMed Central  Google Scholar 

  34. Joshipura KJ, Douglass CW, Garcia RI, Valachovic R, Willett WC (1996) Validity of a self-reported periodontal disease measure. J Public Health Dent 56:205–212

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Joshipura KJ, Pitiphat W, Douglass CW (2002) Validation of self-reported periodontal measures among health professionals. J Public Health Dent 62:115–121

    PubMed  Google Scholar 

  36. Douglass CW, Berlin J, Tennstedt S (1991) The validity of self-reported oral health status in the elderly. J Public Health Dent 51:220–222

    CAS  PubMed  Google Scholar 

  37. Feskanich D, Rimm EB, Giovannucci EL et al (1993) Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J Am Diet Assoc 93:790–796

    CAS  PubMed  Google Scholar 

  38. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC (1992) Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol 135:1114–26 (discussion 27–36)

    CAS  PubMed  Google Scholar 

  39. Chiuve SE, Fung TT, Rimm EB et al (2012) Alternative dietary indices both strongly predict risk of chronic disease. J Nutr 142:1009–1018

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Dorkin TJ, Robson CN, Neal DE (1997) The molecular pathology of urological malignancies. J Pathol 183:380–387

    CAS  PubMed  Google Scholar 

  41. Cox DR, Oakes D (1984) Analysis of survival data. Chapman and Hall, London, New York

    Google Scholar 

  42. Basaran UN, Celayir S, Eray N, Ozturk R, Senyuz OF (1998) The effect of an H2-receptor antagonist on small-bowel colonization and bacterial translocation in newborn rats. Pediatr Surg Int 13:118–120

    CAS  PubMed  Google Scholar 

  43. Rink M, Crivelli JJ, Shariat SF, Chun FK, Messing EM, Soloway MS (2015) Smoking and bladder cancer: a systematic review of risk and outcomes. Eur Urol Focus 1:17–27

    PubMed  Google Scholar 

  44. Srinivas V, Khan SA, Hoisington S, Varma A, Gonder MJ (1986) Relationship of blood groups and bladder cancer. J Urol 135:50–52

    CAS  PubMed  Google Scholar 

  45. Meyer MS, Joshipura K, Giovannucci E, Michaud DS (2008) A review of the relationship between tooth loss, periodontal disease, and cancer. Cancer Causes Control 19:895–907

    PubMed  PubMed Central  Google Scholar 

  46. Chan FK, Leung WK (2002) Peptic-ulcer disease. Lancet 360:933–941

    PubMed  Google Scholar 

  47. Caygill CP, Hill MJ, Hall CN, Kirkham JS, Northfield TC (1987) Increased risk of cancer at multiple sites after gastric surgery for peptic ulcer. Gut 28:924–928

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Lundegardh G, Adami HO, Helmick C, Zack M (1994) Risk of cancer following partial gastrectomy for benign ulcer disease. Br J Surg 81:1164–1167

    CAS  PubMed  Google Scholar 

  49. Leach SA, Thompson M, Hill M (1987) Bacterially catalysed N-nitrosation reactions and their relative importance in the human stomach. Carcinogenesis 8:1907–1912

    CAS  PubMed  Google Scholar 

  50. Farinati F, Della Libera G, Cardin R et al (1996) Gastric antioxidant, nitrites, and mucosal lipoperoxidation in chronic gastritis and Helicobacter pylori infection. J Clin Gastroenterol 22:275–281

    CAS  PubMed  Google Scholar 

  51. Slots J, Ting M (2000) (1999) Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontol 20:82–121

    Google Scholar 

  52. Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809–1820

    PubMed  Google Scholar 

  53. Li X, Kolltveit KM, Tronstad L, Olsen I (2000) Systemic diseases caused by oral infection. Clin Microbiol Rev 13:547–558

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank the participants and staff of the HPFS for their valuable contributions, as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.

Funding

This work was supported by the National Institutes of Health (R01 HL35464 and UM1 CA167552). HO is supported by a Korea University Grant K1808781; NK was supported by grants from the National Research Foundation of Korea (NRF-2018R1C1B6008822; NRF-2018R1A4A1022589).

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Author notes

  1. Hannah Oh and Dong Hoon Lee have contributed equally to this work.

Authors and Affiliations

  1. Division of Health Policy and Management, College of Health Sciences, Korea University, Seoul, South Korea

    Hannah Oh

  2. Department of Public Health Sciences, Graduate School, Korea University, Seoul, South Korea

    Hannah Oh

  3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Dong Hoon Lee, Edward L. Giovannucci & NaNa Keum

  4. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Edward L. Giovannucci

  5. Department of Food Science and Biotechnology, DongGuk University, SangMyung building Room 543, Siksa-dong, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, South Korea

    NaNa Keum

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Contributions

All authors had full access to all of the data and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: All authors. Acquisition, analysis or interpretation of data: All authors. Original draft preparation: Hannah Oh. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Dong Hoon Lee and NaNa Keum. Study supervision: NaNa Keum.

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Correspondence to NaNa Keum.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Oh, H., Lee, D.H., Giovannucci, E.L. et al. Gastric and duodenal ulcers, periodontal disease, and risk of bladder cancer in the Health Professionals Follow-up Study. Cancer Causes Control 31, 383–391 (2020). https://doi.org/10.1007/s10552-020-01274-4

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