Abstract
Purpose
Periodontitis, a chronic inflammatory response to pathogenic bacteria in the oral microbiome, is common among adults. It is associated with several medical conditions, including cardiovascular diseases, and potentially with esophageal, lung, oral, and pancreatic cancer. One of the proposed mechanisms behind these associations is systemic inflammation, which has also been implicated in ovarian cancer etiology. The aim of this study was to evaluate association between ovarian cancer and periodontal bone loss.
Methods
The association between periodontal bone loss, a marker of periodontitis, and risk of epithelial ovarian cancer was estimated among 60,560 participants of the prospective Nurses’ Health Study using Cox proportional hazards analysis. Competing risks analysis was used to estimate association by histologic subtype.
Results
We did not observe an increased risk of ovarian cancer among participants with periodontal bone loss (HR 0.86, 95 % CI 0.64–1.15). Among women younger than 69 years, periodontal bone loss was associated with a 40 % (HR 0.60, 95 % CI 0.36–0.98) decreased ovarian cancer risk, while there was no association in women older than 69 (HR 1.09, 95 % CI 0.75–1.58), although this difference did not reach statistical significance (p-heterogeneity = 0.06). We observed a suggestive decreased risk for serous tumors (HR 0.76, 95 % CI 0.53–1.09). The number of natural teeth and root canals, other metrics of oral health, were not associated with ovarian cancer risk.
Conclusion
Our results do not support an increased ovarian cancer risk in women with periodontal bone loss; however, there was a significant decrease in risk in women younger than 69. Given the unexpected association between periodontal bone loss and ovarian cancer risk in younger women, further research is warranted.
References
American Cancer Society (2014) Cancer facts and figures 2014. American Cancer Society, Atlanta
Cramer DW, Welch WR (1983) Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis. J Natl Cancer Inst 71:717–721
Fathalla MF (1971) Incessant ovulation—a factor in ovarian neoplasia? Lancet 2:163
Risch HA (1998) Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst 90:1774–1786
Ness RB, Cottreau C (1999) Possible role of ovarian epithelial inflammation in ovarian cancer. J Natl Cancer Inst 91:1459–1467
Poole EM, Lee IM, Ridker PM, Buring JE, Hankinson SE, Tworoger SS (2013) A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels and risk of ovarian cancer. Am J Epidemiol 178:1256–1264
Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ (2012) Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res 91:914–920
Papapanou PN (1996) Periodontal diseases: epidemiology. Ann Periodontol 1:1–36
Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809–1820
Joshipura KJ, Wand HC, Merchant AT, Rimm EB (2004) Periodontal disease and biomarkers related to cardiovascular disease. J Dent Res 83:151–155
Moutsopoulos NM, Madianos PN (2006) Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections. Ann N Y Acad Sci 1088:251–264
Fitzpatrick SG, Katz J (2010) The association between periodontal disease and cancer: a review of the literature. J Dent 38:83–95
Bascones-Martinez A, Gonzalez-Febles J, Sanz-Esporrin J (2014) Diabetes and periodontal disease. Review of the literature. Am J Dent 27:63–67
Demmer RT, Desvarieux M (2006) Periodontal infections and cardiovascular disease: the heart of the matter. J Am Dent Assoc 137:14S–20S
Huck O, Tenenbaum H, Davideau JL (2011) Relationship between periodontal diseases and preterm birth: recent epidemiological and biological data. J Pregnancy 2011:164654
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
Nakib S, Han J, Li T, Joshipura K, Qureshi AA (2013) Periodontal disease and risk of psoriasis among nurses in the United States. Acta Odontol Scand 71:1423–1429
Colditz GA, Hankinson SE (2005) The Nurses’ Health Study: lifestyle and health among women. Nat Rev Cancer 5:388–396
McCullough ML, Feskanich D, Stampfer MJ, Giovannucci EL, Rimm EB, Hu FB et al (2002) Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance. Am J Clin Nutr 76:1261–1271
Bertrand KA, Giovannucci E, Liu Y, Malspeis S, Eliassen AH, Wu K et al (2012) Determinants of plasma 25-hydroxyvitamin D and development of prediction models in three US cohorts. Br J Nutr 108:1889–1896
Lunn M, McNeil D (1995) Applying Cox regression to competing risks. Biometrics 51:524–532
Beral V, Gaitskell K, Hermon C, Moser K, Reeves G, Peto R (2012) Ovarian cancer and smoking: individual participant meta-analysis including 28,114 women with ovarian cancer from 51 epidemiological studies. Lancet Oncol 13:946–956
Preshaw PM (2013) Oral contraceptives and the periodontium. Periodontol 2000(61):125–159
Taguchi A, Sanada M, Suei Y, Ohtsuka M, Nakamoto T, Lee K et al (2004) Effect of estrogen use on tooth retention, oral bone height, and oral bone porosity in Japanese postmenopausal women. Menopause 11:556–562
Genco RJ, Borgnakke WS (2013) Risk factors for periodontal disease. Periodontol 2000(62):59–94
Ng N, Kaye EK, Garcia RI (2014) Coffee consumption and periodontal disease in males. J Periodontol 85:1042–1049
Riggs BL, Khosla S, Melton LJ 3rd (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 13:763–773
Risch HA, Howe GR (1995) Pelvic inflammatory disease and the risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 4:447–451
Chang WI, Chang JY, Kim YY, Lee G, Kho HS (2011) MUC1 expression in the oral mucosal epithelial cells of the elderly. Arch Oral Biol 56:885–890
Ho SB, Niehans GA, Lyftogt C, Yan PS, Cherwitz DL, Gum ET et al (1993) Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res 53:641–651
Liu B, Lague JR, Nunes DP, Toselli P, Oppenheim FG, Soares RV et al (2002) Expression of membrane-associated mucins MUC1 and MUC4 in major human salivary glands. J Histochem Cytochem 50:811–820
Li X, Wang L, Nunes DP, Troxler RF, Offner GD (2003) Pro-inflammatory cytokines up-regulate MUC1 gene expression in oral epithelial cells. J Dent Res 82:883–887
Kesavalu L, Chandrasekar B, Ebersole JL (2002) In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol 17:177–180
Rouabhia M, Ross G, Page N, Chakir J (2002) Interleukin-18 and gamma interferon production by oral epithelial cells in response to exposure to Candida albicans or lipopolysaccharide stimulation. Infect Immun 70:7073–7080
Cramer DW, Titus-Ernstoff L, McKolanis JR, Welch WR, Vitonis AF, Berkowitz RS et al (2005) Conditions associated with antibodies against the tumor-associated antigen MUC1 and their relationship to risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 14:1125–1131
Croce MV, Isla-Larrain MT, Price MR, Segal-Eiras A (2001) Detection of circulating mammary mucin (Muc1) and MUC1 immune complexes (Muc1-CIC) in healthy women Int. J Biol Markers 16:112–120
Pinheiro SP, Hankinson SE, Tworoger SS, Rosner BA, McKolanis JR, Finn OJ et al (2010) Anti-MUC1 antibodies and ovarian cancer risk: prospective data from the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev 19:1595–1601
Kumar R, Burns EA (2008) Age-related decline in immunity: implications for vaccine responsiveness. Expert Rev Vaccines 7:467–479
Joshipura KJ, Pitiphat W, Douglass CW (2002) Validation of self-reported periodontal measures among health professionals. J Public Health Dent 62:115–121
Acknowledgments
This work was supported by the National Cancer Institute at the National Institutes of Health (UM1 CA186107, P01 CA87969, 5T32CA009001-38) and the Department of Defense (W81XWH-10-1-0280). We would like to thank the participants and staff of the Nurses’ Health Study 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.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Babic, A., Poole, E.M., Terry, K.L. et al. Periodontal bone loss and risk of epithelial ovarian cancer. Cancer Causes Control 26, 941–947 (2015). https://doi.org/10.1007/s10552-015-0575-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-015-0575-7