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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 3  |  Page : 527-531

Tooth agenesis: A susceptible indicator for colorectal cancer?


Department of Oral and Maxillofacial Pathology, Farooqia Dental College and Hospital, Mysore, Karnataka, India

Date of Web Publication12-Jun-2018

Correspondence Address:
Dr. Lubna Firdose Begum
Top Floor, No. 08, II Stage, Christian Colony, Rajiv Nagar, Mysore - 570 019, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.168997

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 > Abstract 


Context/Background: Tooth agenesis (excluding third molars) is a common congenital disorder that affects 2.2–10% of the general population. A number of different genes have been shown to be associated with cases of tooth agenesis including AXIN2, IRF6, FGFR1, MSX1, PAX9, and TGFA. Wingless/integration signaling gene, AXIN2, is linked to tooth agenesis and also to colorectal cancer (CRC).
Aims: To analyze the correlation between tooth agenesis and CRC.
Materials and Methods: The study included 50 individuals, who were divided into two groups. Group A: 25 individuals diagnosed with CRC and Group B: 25 individuals as a control group. The clinical details were recorded using preformed questionnaire, approved by ethical committee. Orthopantomogram was obtained for all the cases and controls.
Results: We observed that 16% of cases and 8% of controls reported having tooth agenesis and there was no statistical significance of difference between them (P = 0.384). Among the study group, 4% reported oligodontia and 12% cases reported hypodontia. In the control group 8% reported hypodontia, there was no incidence of oligodontia. Additional finding in the study group was that 24% cases had fissured tongue which was not seen in the control group.
Conclusion: Individuals with tooth agenesis might have an increased risk for CRC. A larger epidemiological study along with genetic mapping and gene sequencing is necessary to rule out the risk and relationship between tooth agenesis and CRC.

Keywords: AXIN2, colorectal cancer, tooth agenesis


How to cite this article:
Paranjyothi M V, Kumaraswamy K L, Begum LF, Manjunath K, Litha, Basheer S. Tooth agenesis: A susceptible indicator for colorectal cancer?. J Can Res Ther 2018;14:527-31

How to cite this URL:
Paranjyothi M V, Kumaraswamy K L, Begum LF, Manjunath K, Litha, Basheer S. Tooth agenesis: A susceptible indicator for colorectal cancer?. J Can Res Ther [serial online] 2018 [cited 2020 Jul 9];14:527-31. Available from: http://www.cancerjournal.net/text.asp?2018/14/3/527/168997




 > Introduction Top


Odontogenesis is a highly coordinated and complex process initiated by the interaction between oral ectoderm and ectomesenchyme.[1] Tooth agenesis, the developmental disorder of congenitally missing teeth, is clinically a heterogeneous condition that may affect a single tooth or multiple teeth.[2],[3],[4],[5] Mutations in the MSX1, PAX9, and AXIN2 genes have been implicated in tooth agenesis.

Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide.[6],[7]MSX1, PAX9, and AXIN2 genes has been associated with CRC.[7]

The reported association between AXIN2 variants, CRC, and tooth agenesis suggests that these conditions may be interlinked.

The aim of the study was to analyze the correlation between tooth agenesis and CRC and to determine if congenitally missing teeth may occur more commonly in individuals diagnosed with CRC than in individuals without this diagnosis.


 > Materials and Methods Top


Our study included two groups A and B, each consisting of 25 individuals. Group A: 25 individuals were diagnosed with CRC, and Group B: 25 individuals were taken as a control without CRC. Twenty-five CRC positive, nonsyndromic patients, were selected randomly from the Bharat Hospital and Institute of Oncology, Mysore, India. After ethical clearance, patients were briefed about the objective of the study and informed consent was obtained before the oral examination.

Detailed medical case history was recorded with a preformed questionnaire, a complete intraoral examination was done, and Panaromic radiograph was taken [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]. All patients were examined under the same circumstances and at the same place by the single professional to avoid Interexaminer bias. The frequency of missing teeth between cases and controls were compared using Pearson's Chi-squared test. All statistical analysis were conducted using SSPSS for Windows, Version 21.0, (Armonk, NY: IBM Corp).
Figure 1: Clinical photograph showing missing 12, 22

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Figure 2: Clinical photograph showing missing upper lateral incisors

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Figure 3: Clinical photograph showing missing 34

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Figure 4: Panoramic radiograph showing missing 12 and 22

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Figure 5: Panoramic radiograph showing the absence of upper lateral incisors

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Figure 6: Panoramic radiograph showing the absence of lower right premolar

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Figure 7: H and E section showing Adeno-carcinoma of colon

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Figure 8: H and E section showing carcinoma of colon

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 > Results Top


In our study between the control and study group, we observed that 16% of cases and 8% of controls reported having tooth agenesis and there was no statistical significance of difference between them (P = 0.384). Among the study group, 4% reported oligodontia and 12% cases reported hypodontia. In the control group 8% reported hypodontia, there was no incidence of oligodontia [Table 1] and [Table 2]. Additional finding in the study group was that 24% cases had fissured tongue which was not seen in the control group.
Table 1: Self-reported missing teeth in study participants

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Table 2: Positive group tabulation

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 > Discussion Top


Odontogenesis is initiated by the interaction between oral ectoderm and ectomesenchyme. The main proteins involved in tooth development belong to one of five signaling pathways including a notch, bone morphogenetic protein, fibroblast growth factor, sonic hedgehog, and wingless/integration (WNT).[8] The earliest mesenchymal markers for tooth formation are the Lim - homeobox domain genes [9] which are expressed in the neural crest ectomesenchyme of the oral half of first branchial arch as early as day 9 of IU life.[9],[10]

Tooth agenesis is one of the most common anomalies of the human dentition, characterized by the developmental absence of one or more teeth. Agenesis of permanent teeth in the general population (excluding third molars) ranges from 2.2% to 10%.[11] The mandibular second premolar is the most commonly affected tooth (2.9–3.2%), followed by the maxillary lateral incisor (1.6–1.8%), and the maxillary second premolar (1.4–1.6%).[5]

A number of terms are used to describe this condition, such as hypodontia, oligodontia, and anodontia. Hypodontia is the term used to describe the absence of one to six teeth, oligodontia is used to describe the absence of more than six teeth, and anodontia the complete absence of teeth.[14]

By the discovery of an association between colon polyps and cancer with tooth agenesis, several investigators have examined the potential for a colon neoplasia predisposition and WNT-signaling pathways genes.[8] The Wnt-signaling pathways are a group of signal transduction pathways made of proteins that pass signals from outside of a cell through cell surface receptors to the inside of the cell. Three Wnt-signaling pathways have been characterized: The canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three Wnt-signaling pathways are activated by the binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the protein inside the cell. Wnt-signaling has been implicated in the regulation of diverse developmental events, as well as in aberrations of cell homeostasis that may lead to cancer.[12],[13] The reported association between AXIN2 variants, CRC, and tooth agenesis suggests that these conditions may be associated. Studies have shown that mutation in a gene called AXIN2, located on chromosome 17, seems to disrupt tooth development early in life and later contributes to the emergence of polyps and eventually colon cancer.[14]

The exact etiopathogenesis of CRC is not known, many factors have been associated with the cause of CRC which includes the increased risk factors such as diet rich in fat and red meat may increase disease risk, heavy alcohol use, as well as smoking, may contribute to a colon cancer. Health factors such as obesity, diabetes, and lack of exercise are associated with increased risk.[15] Most studies point toward genetic abnormality which include mutation in MSX1, PAX9, and AXIN2 genes.

AXIN2 mutations have been regarded as cause for CRC and tooth agenesis.[16] Several studies have shown the predisposition to colon neoplasia and WNT-signaling pathway genes from different perspectives. In our study, the prevalence of dental agenesis among the CRC patients was higher than that of non-CRC patients, but the difference was not statistically significant. It does not, however, rule out the likelihood that a small percentage of individuals may have germline variants in genes that predisposed them to both missing teeth and CRC. With or without the presence of tooth agenesis as part of the clinical phenotype AXIN2 gene variants may have a role in CRC.

In a study of 55 Caucasians from Poland by Mostowska et al., it was found that there was an increased risk of tooth agenesis in individuals carrying the AXIN2 c. 956 +16G allele and the c. 2062 T allele.[17] In a study by Peterlongo et al., on 82 CRC families, they found 29 DNA variants of AXIN2 mutations, none of which were likely to be pathogenic.[18] An association between missing incisors and one of three intragenic polymorphisms in the AXIN2 gene was found in a study by Callahan et al. The missense mutation in exon 10 (P50S, rs2240308) was significant with a P = 0.037. Their study suggested a relationship between AXIN2, its genetic variants, tooth agenesis, and CRC.[19],[20]

An epidemiologic study from the year 2008 found a highly significant increase of congenital tooth agenesis in women with ovarian cancer suggesting that a common genetic etiology may predispose women to both conditions. Tooth agenesis can be used as a marker for susceptibility to ovarian cancer.[21]

Scheper et al. reported a case of Cowden syndrome with multiple hamartomas, fissured tongue, high risk of cancer development, and iron deficiency anemia.[22] In our present study, we noticed fissured tongue in 24% of study group. The high incidence of fissured tongue in our study could prove to be significant, but the effect of cancer therapy on the tongue could also explain the high rate.

Lindor et al. reported a failure of formation of approximately 3–10% of one or more of permanent teeth in their study. They also found that 0.16% individuals in their study reported true oligodontia, consistent with the existing epidemiological data. Overall their study did not provide support for there being a general predisposition to missing teeth among a large cohort of CRC patients.[8] It also presents variable prevalence rates among different ethnic backgrounds; therefore, the use of family-based studies may allow detection of segregation between different phenotypes and improve the likelihood of gene discovery in affected families.

One might still find oligodontia as a marker for colorectal neoplasia if a population of people with oligodontia were surveyed for cancer risks, but that oligodontia is so uncommon as not to be appreciable in a small study. The results were in concordance with the previous studies.


 > Conclusion Top


Individuals with tooth agenesis might have an increased risk for CRC. Individuals with tooth agenesis may undergo periodic screening and take precautionary measures to avoid incidence of CRC. A larger epidemiological study along with genetic mapping and gene sequencing is necessary to rule out the risk and relationship between tooth agenesis and CRC.

Acknowledgment

The authors are thankful to the Faculty of Bharat Hospital and Institute of Oncology, Mysore. And K.R Hospital Mysore for providing the necessary facilities and for their cooperation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Kaushal A, Kamboj M. Odontogenesis – A highly complex cell-cell interaction process. Biomed Electron Biomed Inform 2009;2:143-7.  Back to cited text no. 1
    
2.
De Coster PJ, Marks LA, Martens LC, Huysseune A. Dental agenesis: Genetic and clinical perspectives. J Oral Pathol Med 2009;38:1-17.  Back to cited text no. 2
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Matalova E, Fleischmannova J, Sharpe PT, Tucker AS. Tooth agenesis: From molecular genetics to molecular dentistry. J Dent Res 2008;87:617-23.  Back to cited text no. 3
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Nieminen P. Genetic basis of tooth agenesis. J Exp Zool B Mol Dev Evol 2009;312B: 320-42.  Back to cited text no. 4
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Stavropoulos D, Bartzela T, Bronkhorst E, Mohlin B, Hagberg C. Dental agenesis patterns of permanent teeth in Apert syndrome. Eur J Oral Sci 2011;119:198-203.  Back to cited text no. 5
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Johns LE, Houlston RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol 2001;96:2992-3003.  Back to cited text no. 6
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Lindor NM, Win AK, Gallinger S, Daftary D, Thibodeau SN, Silva R, et al. Colorectal cancer and self-reported tooth agenesis. Hered Cancer Clin Pract 2014;12:7.  Back to cited text no. 8
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Nanci A. Tencate's Oral Histology. 7th ed. New Delhi: Mosby Elsevier; 2008. p. 70-80.  Back to cited text no. 9
    
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Menezes R, Marazita ML, Goldstein McHenry T, Cooper ME, Bardi K, Brandon C, et al. AXIS inhibition protein 2, orofacial clefts and a family history of cancer. J Am Dent Assoc 2009;140:80-4.  Back to cited text no. 10
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Polder BJ, Van't Hof MA, Van der Linden FP, Kuijpers-Jagtman AM. A meta-analysis of the prevalence of dental agenesis of permanent teeth. Community Dent Oral Epidemiol 2004;32:217-26.  Back to cited text no. 11
    
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Kestler HA, Kühl M. From individual Wnt pathways towards a Wnt signalling network. Philos Trans R Soc Lond B Biol Sci 2008;363:1333-47.  Back to cited text no. 12
    
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Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004;20:781-810.  Back to cited text no. 13
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Longtin R. Chew on this: Mutation may be responsible for tooth loss, colon cancer. J Natl Cancer Inst 2004;96:987-9.  Back to cited text no. 14
    
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Campos FG, Logullo Waitzberg AG, Kiss DR, Waitzberg DL, Habr-Gama A, Gama-Rodrigues J. Diet and colorectal cancer: Current evidence for etiology and prevention. Nutr Hosp 2005;20:18-25.  Back to cited text no. 15
    
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Lammi L, Arte S, Somer M, Jarvinen H, Lahermo P, Thesleff I, et al. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 2004;74:1043-50.  Back to cited text no. 16
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Mostowska A, Biedziak B, Jagodzinski PP. Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis. J Hum Genet 2006;51:262-6.  Back to cited text no. 17
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Peterlongo P, Howe LR, Radice P, Sala P, Hong YJ, Hong SI, et al. Germline mutations of AXIN2 are not associated with nonsyndromic colorectal cancer. Hum Mutat 2005;25:498-500.  Back to cited text no. 18
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Matalova E, Fleischmannova J, Sharpe PT, Tucker AS. Tooth agenesis: From molecular genetics to molecular dentistry. J Dent Res 2008;87:617-23.  Back to cited text no. 19
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Callahan N, Modesto A, Meira R, Seymen F, Patir A, Vieira AR. Axis inhibition protein 2 (AXIN2) polymorphisms and tooth agenesis. Arch Oral Biol 2009;54:45-9.  Back to cited text no. 20
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Bonds J, Pollan-White S, Xiang L, Mues G, D'Souza R. Is there a link between ovarian cancer and tooth agenesis? Eur J Med Genet 2014;57:235-9.  Back to cited text no. 21
    
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Scheper MA, Nikitakis NG, Sarlani E, Sauk JJ, Meiller TF. Cowden syndrome: Report of a case with immunohistochemical analysis and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:625-31.  Back to cited text no. 22
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

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