title: Periodontal disease and risk of all cancers among male never smokers: an updated analysis of the Health Professionals Follow-up Study.
abstract: Periodontal disease has a direct impact on the immune response and has been linked to several chronic diseases, including atherosclerosis and stroke. Few studies have examined the association between periodontal disease and cancer.
  
  
  
  A total of 19 933 men reported being never smokers (of cigarette, pipes or cigars) in the Health Professionals' Follow-up Study. Periodontal disease status and teeth number were self-reported at baseline and during follow-up. All cancers were ascertained during 26 years of follow-up. Cox's proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) adjusting for risk factors.
  
  
  
  A 13% increase in total cancer was observed among men reporting periodontitis at baseline, and a 45% increase in risk was observed among men with advanced periodontitis (periodontitis with <17 remaining teeth). Periodontitis was not associated with prostate cancer, colorectal cancer or melanoma, the three most common cancers in this cohort of never smokers, but a 33% increase in risk was observed for smoking-related cancers (lung, bladder, oropharnygeal, esophageal, kidney, stomach and liver cancers; HR = 1.33, 95% CI 1.07-1.65). Men with advanced periodontitis had an HR of 2.57 (95% CI 1.56-4.21; P = 0.0002) for smoking-related cancers, compared with men who did not have periodontitis and had 17 teeth or more. Advanced periodontitis was associated with elevated risks of esophageal and head and neck cancers (HR = 6.29, 95% CI 2.13-18.6; based on five cases with advanced periodontitis) and bladder cancer (HR = 5.06, 95% CI 2.32-11.0; based on nine cases with advanced periodontitis).
  
  
  
  Advanced periodontitis was associated with a 2.5-fold increase in smoking-related cancers among never smokers. Periodontitis may impact cancer risk through system immune dysregulation. Further studies need to examine the immune impact of advanced periodontitis on cancer, especially for cancers known to be caused by smoking.
authors.affiliation: Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston Department of Epidemiology dominique.michaud@tufts.edu.
authors.forename: D S
authors.initials: DS
authors.lastname: Michaud
authors.affiliation: Department of Epidemiology Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence.
authors.forename: K T
authors.initials: KT
authors.lastname: Kelsey
authors.affiliation: Department of Periodontology, Tufts University School of Dental Medicine, Boston.
authors.forename: E
authors.initials: E
authors.lastname: Papathanasiou
authors.affiliation: Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston.
authors.forename: C A
authors.initials: CA
authors.lastname: Genco
authors.affiliation: Department of Nutrition Department of Epidemiology, Harvard School of Public Health, Boston Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, USA.
authors.forename: E
authors.initials: E
authors.lastname: Giovannucci
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D006282:Health Personnel; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D008875:Middle Aged; D010510:Periodontal Diseases / Q000150:complications / Q000453:epidemiology* / Q000473:pathology; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D012307:Risk Factors; D000074285:Smokers; D012907:Smoking / Q000453:epidemiology
keywords: cancer risk; never smokers; periodontal disease
references.citation: Cancer Causes Control. 2013 Jul;24(7):1315-22
references.pmid: 23568534
references.citation: Nature. 2013 Dec 19;504(7480):446-50
references.pmid: 24226770
references.citation: J Clin Gastroenterol. 2014 Nov-Dec;48 Suppl 1:S62-6
references.pmid: 25291131
references.citation: J Public Health Dent. 1991 Fall;51(4):220-2
references.pmid: 1941773
references.citation: Ann Epidemiol. 2003 May;13(5):312-6
references.pmid: 12821269
references.citation: Mol Oral Microbiol. 2010 Oct;25(5):305-16
references.pmid: 20883220
references.citation: Nature. 2013 Dec 19;504(7480):451-5
references.pmid: 24226773
references.citation: Carcinogenesis. 2012 May;33(5):1055-8
references.pmid: 22367402
references.citation: PLoS One. 2014;9(10):e109187
references.pmid: 25299619
references.citation: J Autoimmun. 2010 May;34(3):J258-65
references.pmid: 20042314
references.citation: Nat Rev Immunol. 2015 Jan;15(1):30-44
references.pmid: 25534621
references.citation: Odontology. 2006 Sep;94(1):10-21
references.pmid: 16998613
references.citation: Adv Exp Med Biol. 2014;817:25-38
references.pmid: 24997028
references.citation: J Clin Immunol. 2004 Nov;24(6):617-22
references.pmid: 15622446
references.citation: Cancer Causes Control. 2014 Aug;25(8):1045-53
references.pmid: 24913780
references.citation: Semin Cancer Biol. 2012 Aug;22(4):327-34
references.pmid: 22465232
references.citation: Cancer Causes Control. 2008 Nov;19(9):895-907
references.pmid: 18478344
references.citation: Gut. 2013 Dec;62(12):1764-70
references.pmid: 22990306
references.citation: Am J Epidemiol. 2010 Jan 15;171(2):253-9
references.pmid: 19969528
references.citation: J Public Health Dent. 2002 Spring;62(2):115-21
references.pmid: 11989206
references.citation: J Public Health Dent. 1996 Summer;56(4):205-12
references.pmid: 8906704
references.citation: Clin Epigenetics. 2015 Aug 06;7:81
references.pmid: 26246861
references.citation: Circulation. 2012 May 22;125(20):2520-44
references.pmid: 22514251
references.citation: J Am Heart Assoc. 2013;2(6):e000254
references.pmid: 24166489
references.citation: Mol Oral Microbiol. 2012 Dec;27(6):409-19
references.pmid: 23134607
references.citation: J Natl Cancer Inst. 2004 Jan 21;96(2):99-106
references.pmid: 14734699
references.citation: Cancer J. 2014 May-Jun;20(3):232-6
references.pmid: 24855013
references.citation: Science. 2015 Apr 3;348(6230):80-6
references.pmid: 25838377
references.citation: Adv Dent Res. 2014 May;26(1):23-9
references.pmid: 24736701
references.citation: Sci Rep. 2015;5:9262
references.pmid: 25788457
references.citation: Lancet Oncol. 2008 Jun;9(6):550-8
references.pmid: 18462995