REVIEW PAPER
Effect of tobacco on periodontal disease and oral cancer
Yixin Zhang 1
,  
Jinxiu He 1
,  
Bing He 2
,  
Ruijie Huang# 1
,  
Mingyun Li# 1  
 
 
More details
Hide details
1
State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
2
Protein Section, Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
CORRESPONDING AUTHOR
Ruijie Huang#
State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
Mingyun Li#   

State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China
Publish date: 2019-05-09
 
Tob. Induc. Dis. 2019;17(May):40
KEYWORDS
TOPICS
#Co-correspondence authors
ABSTRACT
Introduction:
Periodontal disease and oral cancer are common health hazards. Epidemiological investigations show that smoking, periodontal disease and oral cancer are closely related. Tobacco is one of the major risk factors for periodontitis and oral cancer.

Methods:
A systematic literature review was performed. To identify relevant studies, the following online databases were searched using specific keywords: PubMed, Web of Science and CNKI.

Results:
Tobacco not only possesses an addictive effect, but it aggravates periodontal disease by promoting the invasion of pathogenic bacteria, inhibiting autoimmune defense, aggravating the inflammatory reaction, and aggravating the loss of alveolar bone. According to current evidence, tobacco significantly aggravates the development and progression of periodontal disease and oral cancer, and periodontal disease may be related to the prevalence of oral cancer.

Conclusions:
Clinicians should strongly recommend that smokers undertake a strategy to stop smoking to avoid the exacerbation of nicotine-related periodontal disease and to reduce the incidence of oral cancer.

CONFLICTS OF INTEREST
Authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported.
FUNDING
This review was supported by the National Natural Science Foundation of China (81400501 to ML, 31800114 to RH and 81500811 to BH).
AUTHORS' CONTRIBUTIONS
YZ, RH and ML contributed to the design, drafting and revision of the review. JH and BH contributed to the revision of the review.
PROVENANCE AND PEER REVIEW
Not commissioned; externally peer reviewed.
 
REFERENCES (109)
1.
Razavi SM, Siadat S, Rahbar P, Hosseini SM, Shirani AM. Trends in oral cancer rates in Isfahan, Iran during 1991-2010. Dent Res J (Isfahan). 2012;9(Suppl 1):S88-S93.
 
2.
Sutton JD, Salas Martinez ML, Gerkovich MM. Environmental Tobacco Smoke and Periodontitis in United States Non-Smokers, 2009 to 2012. J Periodontol. 2017;88(6):565-574. doi:10.1902/jop.2017.160725
 
3.
Akinkugbe AA, Sanders AE, Preisser JS, Cai J, Salazar CR, Beck JD. Environmental tobacco smoke exposure and periodontitis prevalence among nonsmokers in the hispanic community Health Study/Study of Latinos. Community dentistry and oral epidemiology. 2017;45(2):168-177. doi:10.1111/cdoe.12275
 
4.
Akinkugbe AA, Slade GD, Divaris K, Poole C. Systematic Review and Meta-analysis of the Association Between Exposure to Environmental Tobacco Smoke and Periodontitis Endpoints Among Nonsmokers. Nicotine & tobacco research: official journal of the Society for Research on Nicotine and Tobacco. 2016;18(11):2047-2056. doi:10.1093/ntr/ntw105
 
5.
Dietrich T, Walter C, Oluwagbemigun K, et al. Smoking, Smoking Cessation, and Risk of Tooth Loss: The EPIC-Potsdam Study. J Dent Res. 2015;94(10):1369-1375. doi:10.1177/0022034515598961
 
6.
Ozden FO, Ozgonenel O, Ozden B, Aydogdu A. Diagnosis of periodontaldiseases using different classification algorithms: a preliminary study. Niger J Clin Pract. 2015;18(3):416–421. doi:10.4103/1119-3077.151785
 
7.
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809–1820. doi:10.1016/s0140-6736(05)67728-8
 
8.
Genco RB, Borgnakke WS. Risk factors for periodontal disease. Periodontology 2000. 2013;62(1):59-94. doi: 10.1111/j.1600-0757.2012.00457.x
 
9.
Pindborg JJ. Tobacco and gingivitis: Ι. Statistical examination of the significance of tobacco in the development of ulceromembranous gingivitis and in the formation of calculus. J Dent Res. 1947;26:261-264.
 
10.
Pindborg JJ . Tobacco and gingivitis: II. Correlation between consumption of tobacco, ulceromembranous gingivitis and calculus. J Dent Res. 1949;28(5):460-463. doi: 10.1177/00220345490280050601
 
11.
Haber J, Wattles J, Crowley M, Mandell R, Joshipura K, Kent RL. Evidence for cigarette smoking as a major risk factor for periodontitis. J Periodontol. 1993;64(1):16–23. doi:10.1902/jop.1993.64.1.16
 
12.
Vouros ID, Kalpidis C, Chadjipantelis T, Konstantinidis AB. Cigarette smoking associated with advanced periodontal destruction in a Greek sample population of patients with periodontal disease. J Int Acad Periodontol. 2009;11:250–257.
 
13.
Yanagisawa T, Ueno M, Shinada K, Ohara S, Wright FA, Kawaguchi Y. Relationship of smoking and smoking cessation with oral health status in Japanese men. Journal of periodontal research. 2019;45(2):277–283. doi:10.1111/j.1600-0765.2009.01233.x
 
14.
Krall EA, Garvey AJ, Garcia RI. Alveolar bone loss and tooth loss in male cigar and pipe smokers. J Am Dent Assoc. 1999;130(1):57–64. doi:10.14219/jada.archive.1999.0029
 
15.
Leung WK Ng DK, Jin L, Corbet EF. Tooth loss in treated periodontitis patients responsible for their supportive care arrangements. J Clin Periodontol. 2006;33:265–575. doi:10.1111/j.1600-051X.2006.00903.x
 
16.
Flouris AD Koutedakis Y. Immediate and short-term consequences of secondhand smoke exposure on the respiratory system. Curr Opin Pulm Med. 2011;17(2):110-115. doi:10.1097/mcp.0b013e328343165d
 
17.
Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma – an update. CA Cancer J Clin. 2015;65(5):401–421. doi:10.3322/caac.21293
 
18.
Chang TS, Chang CM, Ho HC, et al. Impact of young age on the prognosis for oral cancer: a population-based study in Taiwan. PloS one. 2013;8(9):e75855. doi:10.1371/journal.pone.0075855
 
19.
Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4-5):309-316. doi:10.1016/j.oraloncology.2008.06.002
 
20.
Warnakulasuriya S, Sutherland G, Scully C. Tobacco, oral cancer, and treatment of dependence. Oral Oncol. 2005;41(3):244-260. doi:10.1016/j.oraloncology.2004.08.010
 
21.
Esfahrood ZR, Zamanian A, Torshabi M, Abrishami M. The effect of nicotine and cotinine on human gingival fibroblasts attachment to root surfaces. J Basic Clin Physiol Pharmacol. 2015;26(5):517-522. doi:10.1515/jbcpp-2014-0120
 
22.
Tezal M, Sullivan M, Reid ME, et al. Chronic periodontitis and the risk of tongue cancer. Arch Otolaryngol Head Neck Surg. 2007;133(5):450-454. doi:10.1001/archotol.133.5.450
 
23.
Tezal M, Sullivan MA, Hyland A, et al. Chronic periodontitis and the incidence of head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Preventon. 2009;18(9):2406–2412. doi:10.1158/1055-9965.epi-09-0334
 
24.
Ansai T, TakataY, Yoshida A, et al. Association between tooth loss and orodigestive cancer mortality in an 80-year-old community-dwelling Japanese population: a 12-year prospective study. BMC Public Health. 2013;13(1):814. doi: 10.1186/1471-2458-13-814
 
25.
Rezende CP, Ramos MB, Daguíla CH, Dedivitis RA, Rapoport A. Oral health changes in with oral and oropharyngeal cancer. Braz J Otorhinolaryngol. 2008;74(4):596–600. doi:10.1016/s1808-8694(15)30609-1
 
26.
Rosenquist K, Wennerberg J, Schildt EB, Bladström A, Göran Hansson B, Andersson G. Oral status, oral infections and some lifestyle factors as risk factors for oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden. Acta Otolaryngol. 2005;125(12):1327–1336. doi:10.1080/00016480510012273
 
27.
Chang YC, Huang FM, Tai KW, Yang LC, Chou MY. Mechanisms of cytotoxicity of nicotine in human periodontal ligament fibroblast cultures in vitro.J Periodont Res. 2002;37(4):279-285. doi:10.1034/j.1600-0765.2002.01612.x
 
28.
Lallier TE, Moylan JT, Maturin E. Greater sensitivity of oral fibroblasts to smoked versus smokeless tobacco. Journal of periodontology. 2017;88(12):1356-1365.
 
29.
Du Y, Yong S, Zhou Z, et al. [A preliminary study on the autophagy level of human periodontal ligament cells regulated by nicotine]. West China journal of stomatology. 2017;35(2):198-202. doi:10.7518/hxkq.2017.02.017
 
30.
Zhang W, Song F, Windsor LJ. Effects of Tobacco and P. gingivalis on Gingival Fibroblasts. Journal of Dental Research. 2010;89(5):527-31. doi:10.1177/0022034509358567
 
31.
Zhou J, Olson BL, Windsor LJ. Nicotine increases the collagen-degrading ability of human gingival fibroblast. J Periodont Res. 2007;42:228-235. doi:10.1111/j.1600-0765.2006.00937.x.
 
32.
Deveci B, Ayna B, Tacir IH, Deveci E, Tuncer MC, Pala A. Effects of nicotine administration in rats on MMP2 and VEGF levels in periodontal membrane. Folia morphologica. 2018;77(3):471-477. doi:10.5603/FM.a2018.0004
 
33.
Park GJ, Kim YS, Kang KL, et al. Effects of sirtuin 1 activation on nicotine and lipopolysaccharide-induced cytotoxicity and inflammatory cytokine production in human gingival fibroblasts. Journal of periodontal research. 2013;48(4):483-492 doi:10.1111/jre.12030
 
34.
Thuong NV, Hall LL, Gallacher G, et al. Choline acetyltransferase, acetylcholinesterase, and nicotinic acetylcholine receptors of human gingival and esophageal epithelia. J Dent Res. 2000;79(4):939-949. doi:10.1177/00220345000790040901
 
35.
Brejc K, van Dijk WJ, Klaassen RV, et al. Crystal structure of an ach-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature. 2001;411(6835):269-276. doi:10.1038/35077011
 
36.
Faruk ER, Deveci E, Kalkanli S, Deveci B. The effects of nicotine on the incisive teeth and expression of vimentin in rats. Int. J. Morphol. 2013;31(2):516-519. doi:10.4067/s0717-95022013000200026
 
37.
Moga M, Bosca AB, Soritau O. Nicotine cytotoxicity on the mesenchymal stem cells derived from human periodontium. Romanian biotechnological letters. 2016;21(4):11763-11772.
 
38.
Ng T, Huang L, Cao D, et al. Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials. Scientific reports. 2015;5(1):7828. doi:10.1038/srep07828.
 
39.
White DJ. Dental calculus: recent insights into occurrence, formation, prevention, removal and oral health effects of supragingival and subgingival deposits. Eur J Oral Sci. 1997;105:508-522. doi:10.1111/j.1600-0722.1997.tb00238.x
 
40.
Hutcherson JA, Scott DA, Bagaitkar J. Scratching the surface - tobacco-induced bacterial biofilms. Tob Induc Dis. 2015;13(1):1. doi:10.1186/s12971-014-0026-3
 
41.
Apatzidou DA, Riggio MP, Kinane DF. Impact of smoking on the clinical, microbiological and immunological parameters of adult patients with periodontitis. J Clin Periodontol. 2005;32(9):973-983. doi:10.1111/j.1600-051x.2005.00788.x
 
42.
Salvi GE, Ramseier CA, Kandylaki M, Sigrist L, Awedowa E, Lang NP. Experimental gingivitis in cigarette smokers: a clinical and microbiological study. J Clin Periodontol. 2005;32(5):441-447. doi:10.1111/j.1600-051x.2005.00691.x
 
43.
Cogo K, Montan FM, Bergamaschi CC, Andrade ED, Rosalen PL, Groppo FC. In vitro evaluation of the effect of nicotine, cotinine, and caffeine on oral microorganisms. Canadian journal of microbiology. 2008;54(6):501-508. doi:10.1139/w08-032
 
44.
Haffajee AD, Socransky SS. Relationship of cigarette smoking to the subgingival microbiota. J Clin Periodontol. 2001;28(5):377-388. doi:10.1034/j.1600-051x.2001.028005377.x
 
45.
Huang R, Li M, Ye M, Yang K, Xu X, Gregory RL. Effects of Nicotine on Streptococcus gordonii Growth, Biofilm Formation, and Cell Aggregation. Applied and environmental microbiology. 2014;80(23):7212-7218. doi: 10.1128/AEM.02395-14
 
46.
Shan G, Wan Harun HA. Influence of nicotine on the adherence of Candida albicans ATCC 14053 and Candida parapsilosis ATCC 22019 and expression of selected binding-related genes. Biotechnology & Biotechnological Equipment. 2017:1-8. doi:10.1080/13102818.2017.1334593
 
47.
Grossi SG, Goodson JM, Gunsolley JC, et al. Mechanical therapy with adjunctive minocycline microspheres reduces red-complex bacteria in smokers. J Periodontol. 2007;78(9):1741-1750 doi:10.1902/jop.2007.070118
 
48.
Cogo K, Calvi BM, Mariano FS, Franco GC, Goncalves RB, Groppo FC. The effects of nicotine and cotinine on Porphyromonas gingivalis colonisation of epithelial cells. Archives of oral biology. 2009;54(11):1061-1067 doi:10.1016/j.archoralbio.2009.08.001
 
49.
Liu S, Tian M, Shi L, Pan W, Wang X, Li M. Effect of nicotine and mecamylamine on growth of periodontal pathogens. Journal of international stomatology. 2017;44(4):421-425.
 
50.
Cogo K, de Andrade A, Labate CA, et al. Proteomic analysis of Porphyromonas gingivalis exposed to nicotine and cotinine. Journal of periodontal research. 2012;47(6):766-775. doi:10.1111/j.1600-0765.2012.01494.x
 
51.
Baek O, Zhu W, Kim HC, Lee SW. Effects of nicotine on the growth and protein expression of Porphyromonas gingivalis. The Journal of Microbiology. 2012;50(1):143-148. doi:10.1007/s12275-012-1212-8
 
52.
Bondy-Carey JL, Galicia J, Bagaitkar J, et al. Neutrophils alter epithelial response to Porphyromonas gingivalis in a gingival crevice model. Molecular oral microbiology. 2013;28(2):102-113. doi:10.1111/omi.12008
 
53.
Nakagawa I, Inaba H, Yamamura T, et al. Invasion of epithelial cells and proteolysis of cellular focal adhesion components by distinct types of Porphyromonas gingivalis fimbriae. Infection and immunity. 2006;74(7):3773-3782. doi:10.1128/iai.01902-05
 
54.
Imamura K, Kokubu E, Kita D, Ota K, Ishihara K, Saito A. Cigarette smoke condensate modulates migration of human gingival epithelial cells and their interactions with Porphyromonas gingivalis. Journal of periodontal research. 2015;50(3):411-421. doi:10.1111/jre.12222
 
55.
Imamura K, Kokubu E, Kita D, et al. Role of mitogen-activated protein kinase pathways in migration of gingival epithelial cells in response to stimulation by cigarette smoke condensate and infection by Porphyromonas gingivalis. Journal of periodontal research. 2016;51(5):613-621. doi:10.1111/jre.12341
 
56.
White PC, Hirschfeld J, Milward MR, et al. Cigarette smoke modifies neutrophil chemotaxis, neutrophil extracellular trap formation and inflammatory response-related gene expression. Journal of periodontal research. 2018;53:525-535. doi:10.1111/jre.12542
 
57.
Erdemir EO DI, Duran I, Haliloglu S. Effects of smoking on clinical parameters and the gingival crevicular fluid levels of IL-6 and TNF-alpha in patients with chronic periodontitis. J Clin Periodontol. 2014;31(2):99-104. doi:10.1111/j.0303-6979.2004.00454.x
 
58.
Honda T Domon H, Okui T, Kajita K, Amanuma R, Yamazaki K. Balance of inflammatory response in stable gingivitis and progressive periodontitis lesions. Clin Exp Immunol. 2006;144:35-40. doi:10.1111/j.1365-2249.2006.03028.x
 
59.
Ge X, Liu YF, Wong Y, et al. Impact of nicotine on the interplay between human periodontal ligament cells and CD4+ T cells. Human & experimental toxicology. 2016;35(9):983-990. doi:10.1177/0960327115614383
 
60.
Yanagita M, Mori K, Kobayashi R, et al. Immunomodulation of dendritic cells differentiated in the presence of nicotine with lipopolysaccharide from Porphyromonas gingivalis. European journal of oral sciences. 2012;120(5):408-414. doi: 10.1111/j.1600-0722.2012.00992.x
 
61.
An N, Andrukhov O, Tang Y, et al. Effect of nicotine and porphyromonas gingivalis lipopolysaccharide on endothelial cells in vitro. PloS one. 2014;9(5):e96942. doi:10.1371/journal.pone.0096942
 
62.
Bozkurt FY, Yetkin Ay Z, Sutcu R, Delibas N, Demirel R. Gingival crevicular fluid leptin levels in periodontitis patients with long-term and heavy smoking. J Periodontol. 2006;77(4):634-640. doi:10.1902/jop.2006.050277
 
63.
Hwang SJ. Influence of smoking cessation on periodontal biomarkers in gingival crevicular fluid for 1 year: A case study. Journal of dental hygiene science. 2014;14(4):525-536. doi:10.17135/jdhs.2014.14.4.525
 
64.
Bunaes DF, Mustafa M, Mohamed HG, Lie SA, Leknes KN. The effect of smoking on inflammatory and bone remodeling markers in gingival crevicular fluid and subgingival microbiota following periodontal therapy. Journal of periodontal research. 2017;52(4):713-724. doi:10.1111/jre.12438
 
65.
Moon KA, Rule AM, Magid HS, et al. Biomarkers of Secondhand Smoke Exposure in Waterpipe Tobacco Venue Employees in Istanbul, Moscow, and Cairo. Nicotine & tobacco research: official journal of the Society for Research on Nicotine and Tobacco. 2018;20(4):482-491. doi:10.1093/ntr/ntx125
 
66.
Souto GR, Queiroz-Junior CM, Costa FO, Mesquita RA. Effect of smoking on immunity in human chronic periodontitis. Immunobiology. 2014;219(12):909-915. doi:10.1016/j.imbio.2014.08.003
 
67.
Meenawat A, Govila V, Goel S, et al. Evaluation of the effect of nicotine and metabolites on the periodontal status and the mRNA expression of interleukin-1beta in smokers with chronic periodontitis. Journal of Indian Society of Periodontology. 2015;19(4):381-387. doi:10.4103/0972-124X.157879
 
68.
Johnson GK, Guthmiller JM, Joly S, Organ CC, Dawson DV. Interleukin-1 and interleukin-8 in nicotine- and lipopolysaccharide-exposed gingival keratinocyte cultures. Journal of periodontal research. 2010;45(4):583-588. doi:10.1111/j.1600-0765.2009.01262.x
 
69.
Almasri A, Wisithphrom K, Windsor LJ, Olson B. Nicotine and lipopolysaccharide affect cytokine expression from gingival fibroblasts. J Periodontol. 2007;78(3):533-541. doi:10.1902/jop.2007.060296
 
70.
Xanthoulea S, Deliaert A, Romano A, Rensen SS, Buurman WA, van der Hulst RR. Nicotine effect on inflammatory and growth factor responses in murine cutaneous wound healing. International immunopharmacology. 2013;17(4):1155-1164. doi:10.1016/j.intimp.2013.10.022.
 
71.
Han YK, Lee IS, Lee S. Jak/stat pathway modulates on porphyromonas gingivalis lipopolysaccharide- and nicotine-induced inflammation in osteoblasts. Journal of Dental Hygiene Science. 2017;17(1):81-86. doi:10.17135/jdhs.2017.17.1.81
 
72.
Cho YA, Jue SS, Bae WJ, et al. PIN1 inhibition suppresses osteoclast differentiation and inflammatory responses. J Dent Res. 2015;94(2):371-380. doi:10.1177/0022034514563335
 
73.
Rosa GM, Lucas GQ, Lucas ON. Cigarette smoking and alveolar bone in young adults: a study using digitized radiographs. J Periodontol. 2008;79(2):232-244. doi:10.1902/jop.2008.060522
 
74.
Javed F, Al-Kheraif AA, Rahman I. Comparison of clinical and radiographic periodontal status between habitual water-pipe smokers and cigarette smokers. Journal of periodontology. 2016;87(2):142-147. doi:10.1902/jop.2015.150235
 
75.
Campos ML, Correa MG, Junior FH, Casati MZ, Sallum EA, Sallum AW. Cigarette smoke inhalation increases the alveolar bone loss caused by primary occlusal trauma in a rat model. Journal of periodontal research. 2014;49(2):179-185. doi:10.1111/jre.12091
 
76.
Hapidin H, Othman F, Soelaiman IN, Shuid AN, Luke DA, Mohamed N. Negative effects of nicotine on bone-resorbing cytokines and bone histomorphometric parameters in male rats. Journal of bone and mineral metabolism. 2007;25(2):93-98. doi:10.1007/s00774-006-0733-9
 
77.
Eratilla V, Uysal I, Ozevren H. Effects of nicotineon rat alveolar bone. Analytical and quantitative. Cytopathology and histopathology. 2016;38(5):277-282.
 
78.
Shintcovsk RL, Knop L, Tanaka OM, Maruo H. Nicotine effect on bone remodeling during orthodontic tooth movement: Histological study in rats. Dental Press Journal of Orthodontics. 2014;19(2):96-107. doi:10.1590/2176-9451.19.2.096-107.oar
 
79.
Kirschneck C, Proff P, Maurer M, Reicheneder C, Romer P. Orthodontic forces add to nicotine-induced loss of periodontal bone: An in vivo and in vitro study. Journal of orofacial orthopedics. 2015;76(3):195-212. doi:10.1007/s00056-015-0283-7
 
80.
Chrcanovic BR, Albrektsson T, Wennerberg A. Smoking and dental implants: A systematic review and meta-analysis. Journal of dentistry. 2015;43(5):487-498 doi:10.1016/j.jdent.2015.03.003
 
81.
Bezerra Ferreira JD, Rodrigues JA, Piattelli A, Iezzi G, Gehrke SA, Shibli JA. The effect of cigarette smoking on early osseointegration of dental implants: a prospective controlled study. Clinial oral implants research. 2016;27(9):1123-1128 doi:10.1111/clr.12705
 
82.
Abduljabbar T, Al-Hamoudi N, AlQunayan M. Peri-implant soft-tissue parameters and crestal bone levels among narghile smokers and nonsmokers. Inhalation toxicology. 2017;29(10):457-461. doi:10.1080/08958378.2017.1394401
 
83.
Kubota M, Yanagita M, Mori K, et al. The Effects of Cigarette Smoke Condensate and Nicotine on Periodontal Tissue in a Periodontitis Model Mouse. PloS one. 2016;11(5):e0155594. doi:10.1371/journal.pone.0155594
 
84.
Wu LZ, Duan DM, Liu YF, Ge X, Zhou ZF, Wang XJ. Nicotine favors osteoclastogenesis in human periodontal ligament cells co-cultured with CD4+ T cells by upregulating IL-1β. International Journal of Molecular Medicine. 2013;31(4):938-942. doi:10.3892/ijmm.2013.1259
 
85.
Costa-Rodrigues J, Rocha I, Fernandes MH. Complex osteoclastogenic inductive effects of nicotine over hydroxyapatite. Journal of cellular physiology. 2018;233(2):1029-1040. doi:10.1002/jcp.25956
 
86.
Mody N, Parhami F, Sarafian TA, Demer LL. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free radical biology & medicine. 2001;31(4):509-519. doi:10.1016/s0891-5849(01)00610-4
 
87.
Saito Y, Sato S, Oginuma T, Saito Y, Arai Y, Ito K. Effects of nicotine on guided bone augmentation in rat calvarium. Clinical oral implants research. 2013;24(5):531-535. doi:10.1111/j.1600-0501.2011.02416.x
 
88.
Katono T, Kawato T, Tanabe N, et al. Nicotine treatment induces expression of matrix metalloproteinases in human osteoblastic Saos-2 cells. Acta biochimica et biophysica Sinica. 2006;38(12):874-882. doi:10.1111/j.1745-7270.2006.00240.x
 
89.
Yuhara S, Kasagi S, Inoue A, Otsuka E, Hirose S, Hagiwara H. Effects of nicotine on cultured cells suggest that it can influence the formation and resorption of bone. European journal of pharmacology. 1999;383(3):387-393. doi:10.1016/s0014-2999(99)00551-8
 
90.
Gong M, Liu J, Chou T. Perinatal nicotine exposure disrupts paracrine communication between bone marrow-derived mesenchymal stem cells and alveolar type ii cells transgenerationally. Journal of investigative medicine. 2015;63(1):98.
 
91.
Tura-Ceide O, Lobo B, Paul T, et al. Cigarette smoke challenges bone marrow mesenchymal stem cell capacities in guinea pig. Respiratory research. 2017;18(1):2-12 doi:10.1186/s12931-017-0530-0
 
92.
De Campos JM, Prati AJ, Cirano FR, et al. Smoking modulates gene expression of type i collagen, bone sialoprotein, and osteocalcin in human alveolar bone. Journal of oral and maxillofacial surgery. 2015;73(11):2123-2131. doi:10.1016/j.joms.2015.06.168
 
93.
Saad AYM, Gartner LP, Hiatt JL. Teratogenic effects of nicotine on first molar odontogenesis in the mouse. Acta morphologica hungarica. 1991;39(2):87-96.
 
94.
Wang X, Wen L, Yang F. Effect of nicotine on mouse molar germ development in vitro. Chinese journal of conservative dentistry. 2004;14(3):130-133.
 
95.
Wang X, Wen L, Yang F. The effect of nicotine on BMP secretion of mouse molar germ and dental papilla cells of in vitro. Chinese journal of conservative dentistry. 2004;14(3):134-136.
 
96.
Tanaka K, Miyake Y, Nagata C. Association of prenatal exposure to maternal smoking and postnatal exposure to household smoking with dental caries in 3-year-old Japanese children. Environmental research. 2015;143:148-153. doi:10.1016/j.envres.2015.10.004
 
97.
Hecht S. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer. 2003;3(10):733-744. doi:10.1038/nrc1190
 
98.
Divaris K OA, Smith J, Bell ME, et al. Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head and Neck Cancer Study. Cancer Causes Control. 2010;21(4):567-575. doi:10.1007/s10552-009-9486-9
 
99.
Javed F WS. Is there a relationship between periodontal disease and oral cancer? A systematic review of currently available evidence. Crit Rev Oncol Hematol. 2016;97:197-205. doi:10.1016/j.critrevonc.2015.08.018
 
100.
Meyer MS, Joshipura K, Giovannucci E, Michaud DS. A review of the relationship between tooth loss, periodontal disease, and cancer. Cancer Causes Control. 2008;19(9):895-907. doi:10.1007/s10552-008-9163-4
 
101.
Fitzpatrick SG, Katz, J. The association between periodontal disease and cancer: a review of the literature. J. Dent. 2010;38(2)83-95. doi:10.1016/j.jdent.2009.10.007
 
102.
Ye L, Jiang Y, Liu W, Tao H. Correlation between periodontal disease and oral cancer risk: A meta-analysis. J Can Res Ther. 2016;12(8):237-240. doi:10.4103/0973-1482.200746
 
103.
Yao QW Zhou DS, Peng HJ, Ji P, Liu DS. Association of periodontal disease with oral cancer:a meta-analysis. Tumour Biol. 2014;35(7):7073-7077. doi:10.1007/s13277-014-1951-8
 
104.
Zeng XT, Deng AP, Li C, Xia LY, Niu YM, Leng WD. Periodontal disease and risk of head and neck cancer: a meta-analysis of observational studies. PloS one. 2013;8(10):e79017. doi:10.1371/journal.pone.0079017
 
105.
Javed F, Warnakulasuriya S. Is there a relationship between periodontaldisease and oral cancer? A systematic review of currently available evidence. Crit Rev Oncol Hematol. 2016;97:197-205. doi:10.1016/j.critrevonc.2015.08.018
 
106.
Borgerding M, Klus H. Analysis of complex mixtures-cigarette smoke. Exp Toxicol Pathol. 2005;57(1):43-73. doi:10.1016/j.etp.2005.05.010
 
107.
Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev. 1996;18(2):188-204. doi:10.1093/oxfordjournals.epirev.a017925
 
108.
Ebersole JL, Steffen MJ, Thomas MV, Al-Sabbagh M. Smoking-related cotinine levels and host responses in chronic periodontitis. Journal of periodontal research. 2014;49(5):642-651. doi:10.1111/jre.12146
 
109.
Duque A, Martinez PJ, Giraldo A, et al. Accuracy of cotinine serum test to detect the smoking habit and its association with periodontal disease in a multicenter study. Medicina Oral Patología Oral y Cirugia Bucal. Med Oral Patol Oral Cir Bucal. 2017;22(4):e425-31. doi:10.4317/medoral.21292
 
eISSN:1617-9625