Protocol for assessing maternal, environmental and epigenetic risk factors for dental caries in children

Dental caries affects children and adults alike all over the world. It is a disease of the poor as well as of the rich. Largely preventable, it remains the most prevalent chronic disease among children with a significant impact on individuals, families and society. It has recently been reported that 2.4 billion people globally have untreated dental caries [1]. More than 40 % of preschool and primary school children in Western industrialised countries and other middle income countries, including children in the United States of America [2], Sweden [3], Brazil [4] and Australia [5] experience a high prevalence of dental caries. Despite progress made in caries control over the years by the protective effects of fluoride, increased efforts in oral health promotion, widespread health education, and remarkable advances in treatment options, dental caries remains the most common chronic childhood disease [1]. Among Australian children aged 6–7 years the prevalence of dental caries (treated and untreated combined) was 32.4 % in 2011 [6]. This figure varies by state from 26.5 % in New South Wales to 43.8 %, in Queensland (Table 1) [6]. According to the Queensland Child Oral Health Survey in 2012, 49.5 % of children aged 5–10 had experienced dental caries [7]. More alarmingly, among South East Queensland children this figure was just over 50 % [7]. The mean decayed missing and filled teeth index (dmft) for the same child population was 2.0 with 0.8 teeth being untreated [7]. This worsening situation is despite substantial resources being allocated for prevention and treatment of oral diseases [8].

Oral health is determined by many factors: socio-economic [9], environmental [10], political [11], availability of oral health care facilities [12] and their level of utilization [13]. Furthermore an individual’s health related behaviours [14, 15], as well as oral health knowledge [16], attitudes [17] and practices [16], biological factors [18] including the intrauterine environment [19] and genes [20] have an impact on his/her oral health. Additionally, maternal factors like mother’s level of caries [21, 22], her oral health knowledge [16, 19, 22‐25], salivary loads of cariogenic bacteria [26‐28], salivary characteristics including pH, flow rate and buffering capacity [29, 30], as well as maternal genetics [20] are significant risk indicators to be considered for childhood dental caries. Furthermore, an holistic approach in identifying risk factors risk indicators for dental caries is required as oral health is but a part of general health [31]. Investigating newly emerging risk factors and risk indicators for dental caries is crucial and these can be discovered by studying the natural history of disease and by using modern molecular-based approaches [32]. A conceptual model of how we envision that these factors might interact is presented in Fig. 1.

The importance of inherited factors in susceptibility to dental caries has been recognized for decades [33, 34]. Heritability is the proportion of phenotype variation explained by genetic factors. These have been estimated to account for 30–60 % (p ≤ 0.01) of the variation in caries scores for the permanent dentition and 54–70 % (p ≤ 0.01) for deciduous caries scores [35]. According to Shaffer et al. there is direct evidence for a genetic component in the aetio-pathogenesis of dental caries [36] but very little is known about the specific causal mechanisms [37]. There are many genes related to the composition and structure of dental enamel, inherited alterations in sugar metabolism and genetic regulation of salivary gland function. Unsurprisingly, no single host gene that directly regulates dental caries initiation or progression has been identified [38, 39]. Epigenetics however, may provide the missing link to these unanswered questions [40]. Epigenetics investigates the molecular mechanisms that link genetic and environmental cofactors to disease outcomes [41]. There are many complex mechanisms underlying epigenetic alterations such as DNA methylation, histone modification and gene regulation by non-coding RNA, of which DNA methylation is the most common [42]. Such changes may be heritable or could be environmentally modulated. DNA methylation seems to be the primary mechanism to suppress retro-transposable elements which are responsible for creating genetic variation and, on occasion, disease-causing mutations within the human genome. Because these elements remain partially methylated in sperm, there may be a prolonged period of transposition lasting a few generations before gene expression [43]. Possible epigenetic contributions are currently being investigated in many diseases, but such studies are relatively novel in the dental field [42] and are needed to fully understand DNA-based factors important for development of oral diseases [31].