Destructive effects of smoking on molecular and genetic factors of periodontal disease

Periodontal disease is defined as inflammatory destruction of periodontal tissue and alveolar bone supporting the teeth. Severe and prolonged periodontal inflammation leads to loss of teeth, thereby affecting oral functions (e.g., mastication, speech, and facial esthetics). Progression and severity of the disease depends on complex interactions between several risk factors such as microbial, immunological, environmental, and genetic factors, as well as age, sex, and race [1]. Tobacco smoking is a significant risk factor for periodontal disease [2].Epidemiological studies concerning the association between smoking and periodontal disease have markedly increased since the 1990s. Based on epidemiological articles published from 1965 to 2000, the US Surgeon General's Report 2004, which comprehensively addressed active smoking and health issues, concluded that there is sufficient evidence to infer a causal relationship between smoking and periodontal disease [3]. Although biological plausibility is an important criterion in the Bradford-Hill criteria for assigning causality to an association [4], traditional epidemiology correlates exposure with disease outcomes, and everything between the cause and outcome is treated as a "black box" [5].Despite numerous studies having demonstrated the causal association between smoking and periodontal disease, many questions remain unanswered. For example, what happens when periodontal tissue is exposed to tobacco smoke? How is the onset or progression of periodontal disease in smokers different from that in non-smokers? The underlying mechanisms of smoking-attributed periodontal disease can be further clarified by linking findings of traditional epidemiological studies with those of in vitro studies. Recently, molecular, cellular, and other biological markers (called biomarkers) have been frequently measured in epidemiological studies to reveal the mechanisms and events occurring along the theoretical continuum between exposure to tob