Periodontal Disease and Overall Health: A Clinician's Guide

212 Periodontal Disease and Overall Health: A Clinician's Guideresponse in periodontal disease may lead to asystemic exposure to pro-inflammatory cyto -kines, which in turn may lead to increasedrisk of neoplastic transformation at distantsites. However, the situation may not be assimple as this since most studies investigatingthe link between cancer and inflammationconsider the effect of local inflammationat the site of the cancer rather than systemicelevation of inflammatory mediators. Whileit is possible that elevated systemic levels ofinflammatory cytokines may encourage subthresholdneoplastic states to become neoplastic,local inflammation and local releaseof inflammatory mediators at a site of potentialneoplastic transformation seems morelikely. Alternatively, it has been suggestedthat individuals who suffer from both periodontaldisease and cancer may share similargene polymorphisms in genes encodinginflammatory cytokines; thus periodontitismay merely be a marker of an underlying geneticpredisposing factor rather than a truerisk factor for cancer.InfectionChronic infections have been associatedwith increased cancer risk. For example,bacterial infections such as H. pylori havebeen implicated in gastric cancer as well asHepatitis B and C viral infections implicatedin hepatocellular carcinoma. 40,41Since periodontitis is a chronic infection,it has been postulated that periodontalbacteria within the subgingival plaquebiofilm may be associated with carcinogenesisthrough the release of a multitude oftoxic products (endotoxins, enzymes, hydrogensulfide, ammonia) leading to cell mutationsin tumor suppressor genes and protooncogenesor alter signaling pathways thataffect cell proliferation or cell survival. 18 Inaddition, chronic inflammation induced byperiodontal pathogens results in chronic releaseof pro-inflammatory cytokines, chemo -kines, prostaglandins, growth factors, andenzymes that may have indirect effects oncarcinogenesis by deregulating physiologicalcell turnover and cell growth.In another hypothesis, it has been proposedthat periodontal pathogens may increasethe level of certain carcinogens such asnitrosamines. 32 The formation of endogenousnitrosamines in the oral cavity by nitratereducingbacteria is promoted by poor oralhygiene as well as by tobacco use and certaindietary factors. 51 Increased production of carcinogenicnitrosamines by oral bacteria hasbeen suggested as a possible mechanism foran increased risk of pancreatic cancer in individualswith reported periodontal disease. 2ImmunityPeriodontitis in susceptible patientsmay reflect a failure in the interaction betweenthe innate and adaptive immune responseto clear the bacterial challenge withinthe periodontal pocket. Deregulation of theimmune response may also place an individualat risk of inadequate cellular surveillancefor tumor growth. In particular, thestable periodontal lesion consists of a predominantlyT helper cell 1 (Th l) response 52and is associated with high levels of interferon-(IFN-), an important cytokine incell-mediated immunity and tumor surveillance.53 The progressive periodontitis lesionconsists predominantly of a Th 2 responsewith lower levels of IFN- and a poor innateimmune response. 52 Hence, periodontitis couldmerely be a marker of immune dysfunctionrather than a true risk factor for cancer.CONCLUSIONTo date, only a limited number of studieshave investigated the association betweenperiodontal disease and cancer risk, althoughmany reports have been published concerningthe association between cancer risk andoral condition, oral hygiene, and tooth loss.Positive associations have been demonstratedeven after controlling for known risk factors