To evaluate the potential connection among the numeral of missing teeth and the risk of LC in three private treatments of outpatients in Greece.

Periodontitis; Lung Carcinoma; Cancer risk; Tooth loss; Adults; Chronic inflammation

Lung cancer (LC) is currently the fifth leading cause of death in developed countries [2,3]. The majority of LC cases are genetic factors such as male gender, age, enzyme polymorphism, family history and geneticpredisposition, smoking, behavioral and environmental factors such as inhalation of contaminated air/industrial gas/radon particles and may be due to bad eating habits [2,3].

Chronic inflammation leads to activation of cellular signaling pathways involved in mutagenesis, increased cell proliferation and release of inflammatory biomarkers and other signaling mediators, limited adaptation to oxidative stress, and reactive production.

The possible association between both diseases could be attributed to various reasons as having certain risk factors in common, have as advanced age,cigarette smoking, and low socio-economic status (SES) [43]. One of the biggest challenges in studying periodontitis using observational studies concerns the measurement of PD. Thus, tooth loss can represent several oral conditions, is often only a crude marker of periodontitis, and may vary dramatically depending onthe population, asit has beenshownthatinhealth professionals more than half (58%) had0-16 remaining teeth but did not suffer from periodontitis [23]. Tooth loss is also an SES marker. Missing teeth isattributedto dentalcariesandPD, however, the parameter of age is crucial forthe distribution of all causes, as at an older age the main cause is chronic PD whereasat younger ages themain causeisdentalcaries [6].

Study design

The current report was based on a case-control design and was performed between December 2019 and December 2020. This procedure resulted in a study sample of 605 individuals. Participants enrolled in the study protocol after their selection from three private practices, two medical and one dental, completed a self-administered questionnaire regarding their medical and dental history and their dental clinical examination was carried out by a well-trained and calibrated Dental Surgeon.

Cases and Controls selection criteria

The participants should not have received, during the previous six months, any type of conservative or surgical periodontal treatment, and should not have received any treatment.

Similarly excluded those who received medication or general glucocorticoids for the mentioned pathological conditions. Patients with an advanced stage of LC under treatment such as chemotherapy or radiotherapy, those with metastatic LC, mesothelioma, and patients with aprimary focuson the head-neck-thorax region (carcinogenesis field theory) [47].

The case group consisted of LC patients in whom the diagnosis was based on histological examination after performing their endoscopic procedure.

Medical and Dental Questionnaire

I filled out the Medical Questionnaire [48] at Minnesota Dental School. Subjects were categorized into 4549, 5059, 6069 and 70+by age.

Education level such as elementary school, university/university degree. If the SES is less than 1,000 and more than €1,000/month. Smoking status as a person who has never smoked and as a former/current smoker. Presence or absence of family history of LC and presence of previous lung disease (COPD, TB, ILF).

Clinical examination

Using the standard 28 teeth as a reference, assessing the number of existing teeth and subtracting the number of 28 existing teeth will result in the loss or loss of some teeth. Defined as a tooth.

The clinical assessment of PPD was about immediate complete millimeters. 125 (20%) individuals, cases, and controls, randomly selected, were reexamined for determining the intraexaminer variance, by the same Dental Surgeon and no difference.

Statistical analysis

Mean PPD at 6 sites per subject's teeth was measured and encoded as a dichotomous variable. Male participants, participants with higher educational status (university level) and socioeconomic status (income/monthly>€1,000),active/exsmokers, family history of LC or previous chronic lung disease People, and individuals suffering from LC cases, were also coded as 1 and individuals with moderate and severe periodontal pockets were also coded as 1.

The mean age of the participants, cases and controls, was 64,4 years (± 3.2). Squamous cell carcinoma(SCC) (43.6%), small cell carcinoma(SCLC) (35.4%), adenocarcinoma(AC) (11.2%)and large cell carcinoma (LCC)(9.8%), was the distribution of LC histological types in males, whereas in females the corresponding distribution was AC (47.8%), SCC(36.3%), SCLC (9.7%) and LCC (6.2%).

Table1presents the epidemiological variables according to the univariate analysis and shows that smoking (p=0.000) and previous chronic lung disease (p=0.014), were statistically significantly associated with risk for LC development, whereas PPD (p=0.076)and missing teeth (p=0.065) were not. UOR’s and 95% CI shown in table 1.

Table 1: Univariate analysis of cases and controls regarding each independent variable examined.

By applying a multivariate regression analysis model (Enter and Wald methods), smoking (p=0.000), deep periodontal pockets (p=0.048), and the number of missing teeth greater than 4 are statistically at risk of developing LC. It was shown to be significantly related Table 2. Table 2 also shows AOR and 95% CI.

Table 2: Presentation of association between potentially risk factors and LC according to Enter (first step-1a) and Wald (last step 6a) method of multivariate logistic regression analysis model.

After controlling for possible confounding factors, smoking status and SES, the assessed associations remained significant (Table 3).

Table 3: Smoking status and SES

Current case-control studies have shown that smokers with deep periodontal pockets greater than 4.0 mm and lacking four or more teeth are significantly at increased risk of developing LC. Based on these observations, it may be suggested that smoking cessation and improved oral hygiene may reduce the risk of developing LC. However, further investigation is needed to confirm such results [22,23].On the contrary, similar studies have revealed that females [51,52] and males [53,54] Several studies have used large sample sizes, to increase their out comes precision regarding the association between SES and LC, or cancer in general [83,84]. However, these studies have been influenced by the absence of data on important risk factors for LC [84] or have associated aggregate socioeconomic exposure data to individual-level disease status [83,84]. Delegating characteristics of a group to a person may not be proper and may lead to incorrect outcomes, especially if the exposure to that characteristic, as SES, is inaccurately categorized [85, 86]. The current study recorded no association between educational level and LC risk. Previous reports have revealed a higher risk of malignant diseases, especially smoking-related cancers, among the lowest educationallevel individuals andsupported that the higher the level ofeducational attainment, thelower the LCrisk[72,77,87-89]. On the contrary, Faggianoetal. [90]foundthatLC wasmore frequent in higher social strata, whereas the same author in another report observed that the association between educational level (primary school vs. university) andLC risk wasnegative for males (OR = 2.47) and positive for females (OR= 0.62) [91]. A genetic predisposition has been suggested for developing LC[92,93]. It has been found that regardless of smoking status, individuals with an LC family history had increased risk for developing the disease [94-98]. The findings of the current research did not confirm that suggestion. Pre-existing non-malignant lung diseases such as COPD, chronic bronchitis and emphysema [99], TBC and ILF have been associated with an increased risk for developing LC [100]. COPD is an independentriskfactor for SCC development [101], as those patients showeda 2-5 times higher risk for developingLC, whereasLC occurrenceis uptofive times more probably to have appearedin smokers withairflow obstructionthanthose withnormal lung function [102]. The observationthatCOPDpatientsshowahighprevalence ofLC can be attributed to commonmechanisms such asprematurelung aging, geneticsusceptibilitytobothdiseases or common pathogenic factors, such asgrowthfactors, intracellular signalingpathways activation or epigenetic influences [103]. Tobacco is a shared risk factor of the mentioned lung diseases and LC. The mechanisms by which those lung diseases may independently influence LC risk remain unknown, but ithasbeensuggestedthat inflammation causedby thosediseasesmay act asa catalyst in the development of lung neoplasms[104]. Moreover, little is known about the association between COPD and the risk of developing LC, particularly in non-smokers, as are rarely affected by the disease. Non-smokers COPD patients exposed to indoor pollutants are at higher risk for developing LC [105]. Zheng et al. [66] recorded that individuals with TBC had a 50% increased risk of LC. A study by Hind et al. [67] regarding LC riskamong smokers andnonsmokerswithTBCshowedthatfemaleswith TBC, never-smokers, hadapproximatelyeight times higher risk of LC, whereas no association was foundbetweenfemales smokers. The main limitation of that study was the small number of non-smoking patients with LC [67]. Patients with ILF or other fibrotic diseases had an increased risk of LC, but these potential risk factors have not been accurately identified in nonsmokers [106,107]. No association was recorded in the present report between pre-existing chronic lung disease and risk for LC development. Smoking isa confirmedrisk factor of total cancerand LC [108], as ismainlyinvolved in SCC andSCLC development, andin fewer casesin lungACdevelopment. However, till now the reasons why only 15% of smokers develop LC remain unidentified [109]. The outcomes of the current study confirmed the association examined. Moreover, smoking acts as a confounding factor and is involved in PD development and progression [40]. The outcomes also showed that individuals with deep periodontal pockets were at significantly higher risk for LC. A small number of studies, prospective and based on questionnaires and self-reported data have investigated the possible link between PD indices and LC risk, or total cancer. In a prospective co-twin study [36] was recorded that PD patientshad a higher risk of developing LC, however after adjustment for known confounding factors age, gender, educational level and SES the assessed association was not statistically significant. In another similar study [21] was found that PD patients had an increased risk of total cancer and a significantly increased LC risk, finding that was not confirmed in never smokers. After adjustment for known risk factors for LC, the extent of the association between periodontitis and LC ranged between1.48 and 1.73.

In conclusion, those with deep periodontal pockets and missing four or more teeth had a significantly higher risk of lung cancer. These associations persisted after controlling certain confounding factors such as smoking status and SES.

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