Association between tooth agenesis and cancer: a systematic review

David Normando Corresponding address: David Normando, Rua Augusto Corrêa, 01 - 66075-110 - Belém - Pará - Brazil. Phone: +55 (91) 99144-6316 e-mail: davidnormando@hotmail.com

Universidade Federal do Pará, Faculdade de Odontologia, Belém, Pará, Brasil.

http://orcid.org/0000-0002-1335-1040

Corresponding address: David Normando, Rua Augusto Corrêa, 01 - 66075-110 - Belém - Pará - Brazil. Phone: +55 (91) 99144-6316 e-mail: davidnormando@hotmail.com

*
These authors contributed equally to this work.

Conflicts of interest

There are no conflicts of Interest.

Authors’ contributions

Medina, Melany Clarissa Gomez: Conceptualization (Equal); Data curation (Equal); Formal analysis (Equal); Investigation (Equal); Methodology (Equal); Writing-original draft (Equal). Bastos, Renata Travassos da Rosa Moreira: Conceptualization (Equal); Data curation (Equal); Formal analysis (Equal); Investigation (Equal); Methodology (Equal); Project administration (Equal); Supervision (Equal); Visualization (Equal); Writing-original draft (Equal); Writing-review & editing (Equal). Mecenas, Paulo: Data curation (Equal); Formal analysis (Equal); Investigation (Equal); Methodology (Equal); Validation (Equal); Visualization (Equal); Writing-original draft (Equal); Writing-review & editing (Equal). Pinheiro, João de Jesus Viana: Supervision (Supporting); Writing-review & editing (Equal). Normando, David: Conceptualization (Equal); Project administration (Equal); Supervision (Equal); Writing-review & editing (Equal).

Authors, year, location and type of study	Type of cancer	Sample		Mean Age (years)	Most frequent missing tooth	Family history of cancer control/ case (%)	Genes	Evaluation method	Statistical analysis	Main results
		Without tooth agenesis (with cancer or family history)	With tooth agenesis (with cancer or family history)
Chalothorn et al.,²¹21- Chalothorn LA, Beeman CS, Ebersole JL, Kluemper GT, Hicks EP, Kryscio RJ, et al. Hypodontia as a risk marker for epithelial ovarian cancer: a case-controlled study. J Am Dent Assoc. 2008;139(2):163-9. doi: 10.14219/jada.archive.2008.0132 https://doi.org/10.14219/jada.archive.20... (2008), USA, Case-control	Epithelial Ovarian cancer (EOC)	127 (30)	23 (20)	–	U2, U5	–	–	–	Fisher exact, OR	Possible association between EOC and agenesis. The data also showed that the crude OR was 8.1 (95 percent CI, 2.1-30.9), which implied that women with EOC are 8.1 times more likely to have hypodontia than are women without EOC.
Fekonja et al.,²²22- Fekonja A, Čretnik A, Takač I. Hypodontia prevalence and pattern in women with epithelial ovarian cancer. Angle Orthod. 2014;84(5):810-4. doi: 10.2319/112813-876.1 https://doi.org/10.2319/112813-876.1... (2014), Slovenia, Case-Control	Epithelial Ovarian cancer (EOC)	209 (97)	31 (23)	–	U5, U2, L5, L1	–	–	Clinical and X-rays evaluations	t-test, X², Fisher exact, OR	The difference between the two groups was statistically significant (p=0.004); the crude OR was 3.30 (95% CI, 0.12–7.01). Women with ovarian cancer were 2.87 times (19.2%–6.7%) more likely to have hypodontia than healthy women.
Paranjyothi et al.,²⁴24- Paranjyothi MV, Kumaraswamy KL, Begum LF, Manjunath K, Basheer S. Tooth agenesis: a susceptible indicator for colorectal cancer? J Cancer Res Ther. 2018;14(3):527-31. doi: 10.4103/0973-1482.168997 https://doi.org/10.4103/0973-1482.168997... (2018), India, Case-control	Colorectal cancer (CRC)	44 (21)	6 (4)	–	L5, U2, U5	–	–	Self-reported questionnaire,clinical and X-rays evaluations	X²	Sixteen percent of cancer patients and 8% of individuals without cancer reported having tooth agenesis, no statistical difference (p= 0.384).
Lindor et al.,²⁹29- 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(1):7. doi: 10.1186/1897-4287-12-7 https://doi.org/10.1186/1897-4287-12-7... (2014), Canada, Case-control	Colorectal cancer (CRC)	4188 (1558)	236 (78)	–	–	–	–	Self-reported questionnaire	X², Fisher exact test	4.8% of cases and 5.7% of controls reported having at least one missing tooth, no statistical evidence of difference (p= 0.20).
Williams et al.,³⁰30- Williams MA, Biguetti C, Romero-Bustillos M, Maheshwari K, Dinckan N, Cavalla F, et al. Colorectal cancer-associated genes are associated with tooth agenesis and may have a role in tooth development. Sci Rep. 2018;8(1):2979. doi: 10.1038/s41598-018-21368-z https://doi.org/10.1038/s41598-018-21368... (2018), USA, Case-control	Colorectal cancer (CRC) and family history of any type of cancer	347 (39)	93 (28)	–	–	11,2%/30,1%	ATF1, DUSP10, CASC8	Clinical and radiographic examinations and associated gene variants	–	Genome-wide significant associations were found between TA and ATF1 (P = 4.36 × 10−10) and DUSP10 (P = 1.25 × 10−9), and positive association found with CASC8 (P = 8.2 × 10−5).
Küchler et al.,²⁸28- Küchler EC, Lips A, Tannure PN, Ho B, Costa MC, Granjeiro JM, et al. Tooth agenesis association with self-reported family history of cancer. J Dent Res. 2013;92(2):149-55. doi: 10.1177/0022034512468750 https://doi.org/10.1177/0022034512468750... (2013), USA/Brazil, Case-control	Family history of any type of cancer	328 (102)	82 (45)	Case:18.15 ± 10.2 Control: 20.33 ±14.9	U4, L4, U5, L5, U2, L1, L2	31,1%/54,90%	AXIN2, FGF3, FGF10, FGFR2	Structured questionnaire and clinical and X-rays evaluations	Student's t test, OR, X², Fisher's exact tests	Individuals with tooth agenesis had an increased prevalence of having a family history of cancer OR = 2.7; 95% C.I., 1.6-4.4). A significant association between AXIN2, FGF3, FGF10, and FGFR2 and tooth agenesis was found.

Cancer type or family history	Study	Group	With cancer or family history	Without cancer or family history	Total	OR/95CI (Study)	p-value (study)	OR/95CI (each cancer type or family history)	p-value (each cancer type or family history)
Ovarian cancer	Chalothorn et al.,²¹21- Chalothorn LA, Beeman CS, Ebersole JL, Kluemper GT, Hicks EP, Kryscio RJ, et al. Hypodontia as a risk marker for epithelial ovarian cancer: a case-controlled study. J Am Dent Assoc. 2008;139(2):163-9. doi: 10.14219/jada.archive.2008.0132 https://doi.org/10.14219/jada.archive.20... (2008)	With agenesis	20	3	23	OR: 21.56/5.99-77.58	<0.0001	OR: 6.43/ 3.20- 12.93	<0.0001
		Without agenesis	30	97	127	OR: 21.56/5.99-77.58	<0.0001
	Fekonja et al.,²²22- Fekonja A, Čretnik A, Takač I. Hypodontia prevalence and pattern in women with epithelial ovarian cancer. Angle Orthod. 2014;84(5):810-4. doi: 10.2319/112813-876.1 https://doi.org/10.2319/112813-876.1... (2014)	With agenesis	23	8	31	OR: 3.32/1.42-7.76	0.0070
		Without agenesis	97	112	209	OR: 3.32/1.42-7.76	0.0070
Colorectal cancer	Paranjyothi et al.,²⁴24- Paranjyothi MV, Kumaraswamy KL, Begum LF, Manjunath K, Basheer S. Tooth agenesis: a susceptible indicator for colorectal cancer? J Cancer Res Ther. 2018;14(3):527-31. doi: 10.4103/0973-1482.168997 https://doi.org/10.4103/0973-1482.168997... (2018)	With agenesis	4	2	6	OR: 2.19/0.36-13.22	0.6634	OR: 0.86/ 0.66- 1.13	0.3151
		Without agenesis	21	23	44	OR: 2.19/0.36-13.22	0.6634
	Lindor et al.,²⁹29- 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(1):7. doi: 10.1186/1897-4287-12-7 https://doi.org/10.1186/1897-4287-12-7... (2014)	With agenesis	78	158	236	OR: 0.83/0.63-1.10	0.2240
		Without agenesis	1558	2630	4188	OR: 0.83/0.63-1.10	0.2240
Family history of cancer	Williams et al.,³⁰30- Williams MA, Biguetti C, Romero-Bustillos M, Maheshwari K, Dinckan N, Cavalla F, et al. Colorectal cancer-associated genes are associated with tooth agenesis and may have a role in tooth development. Sci Rep. 2018;8(1):2979. doi: 10.1038/s41598-018-21368-z https://doi.org/10.1038/s41598-018-21368... (2018)	With agenesis	28	65	93	OR: 3.40/1.95-5.92	<0.0001	OR: 2.71/ 1.90- 3.86	<0.0001
		Without agenesis	39	308	347	OR: 3.40/1.95-5.92	<0.0001
	Küchler et al.,²⁸28- Küchler EC, Lips A, Tannure PN, Ho B, Costa MC, Granjeiro JM, et al. Tooth agenesis association with self-reported family history of cancer. J Dent Res. 2013;92(2):149-55. doi: 10.1177/0022034512468750 https://doi.org/10.1177/0022034512468750... (2013)	With agenesis	45	37	82	OR: 2.69/1.64-4.4155	0.0001
		Without agenesis	102	226	338	OR: 2.69/1.64-4.4155	0.0001

Study	Selection (maximum 4 stars)	Comparability (maximum 2 stars)	Outcome or exposure assessment (maximum 3 stars)	Total score (Quality)
Chalothorn et al.,²¹21- Chalothorn LA, Beeman CS, Ebersole JL, Kluemper GT, Hicks EP, Kryscio RJ, et al. Hypodontia as a risk marker for epithelial ovarian cancer: a case-controlled study. J Am Dent Assoc. 2008;139(2):163-9. doi: 10.14219/jada.archive.2008.0132 https://doi.org/10.14219/jada.archive.20... (2008)	3	2	3	8 (Good)
Fekonja et al.,²²22- Fekonja A, Čretnik A, Takač I. Hypodontia prevalence and pattern in women with epithelial ovarian cancer. Angle Orthod. 2014;84(5):810-4. doi: 10.2319/112813-876.1 https://doi.org/10.2319/112813-876.1... (2014)	2	2	3	7 (Fair)
Paranjyothi et al.,²⁴24- Paranjyothi MV, Kumaraswamy KL, Begum LF, Manjunath K, Basheer S. Tooth agenesis: a susceptible indicator for colorectal cancer? J Cancer Res Ther. 2018;14(3):527-31. doi: 10.4103/0973-1482.168997 https://doi.org/10.4103/0973-1482.168997... (2018)	2	1	3	6 (Fair)
Lindor et al.,²⁹29- 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(1):7. doi: 10.1186/1897-4287-12-7 https://doi.org/10.1186/1897-4287-12-7... (2014)	1	2	3	6 (Fair)
Küchler et al.,²⁸28- Küchler EC, Lips A, Tannure PN, Ho B, Costa MC, Granjeiro JM, et al. Tooth agenesis association with self-reported family history of cancer. J Dent Res. 2013;92(2):149-55. doi: 10.1177/0022034512468750 https://doi.org/10.1177/0022034512468750... (2013)	3	2	2	7 (Fair)
Williams et al.,³⁰30- Williams MA, Biguetti C, Romero-Bustillos M, Maheshwari K, Dinckan N, Cavalla F, et al. Colorectal cancer-associated genes are associated with tooth agenesis and may have a role in tooth development. Sci Rep. 2018;8(1):2979. doi: 10.1038/s41598-018-21368-z https://doi.org/10.1038/s41598-018-21368... (2018)	3	2	2	7 (Fair)

[1] Corresponding address: David Normando, Rua Augusto Corrêa, 01 - 66075-110 - Belém - Pará - Brazil. Phone: +55 (91) 99144-6316 e-mail: davidnormando@hotmail.com

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Association between tooth agenesis and cancer: a systematic review

Abstract