Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil
Abstract
:1. Introduction
2. Results
2.1. TP53 R337H Frequency in the Southern Brazilian Population
2.2. TP53 R337H Frequency in Adrenocortical Tumors from Santa Catarina
2.3. Cumulative Incidence of Pediatric ACT in the PR 2006-C Cohort According to Subregion
2.4. Pediatric ACT Incidence Rates in Paraná and Santa Catarina
2.5. Linear Regression (LR) for R337H Frequencies: General Population versus ACT Patients
2.6. ACT Surveillance in Paraná: 2006-C and 2016-C Cohorts
2.7. Revised Estimate of R337H Penetrance in the Paraná 2006-C Cohort
2.8. Age of Pediatric ACT Onset in the PR 2006-C Cohort According to Generation
3. Discussion
4. Materials and Methods
4.1. Genotyping of Newborns for TP53 R337H and Their Cohorts
4.2. TP53 R337H Assay
4.3. ACT Cases from the Cohorts and Public Registry Used to Calculate Incidence
4.4. LR for R337H Frequencies in Three Brazilian States
4.5. TP53 R337H Penetrance in 2006-C Cohort
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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ACT and Carriers | Subregion | |||||||
---|---|---|---|---|---|---|---|---|
C1 | C2 | C3 | Total | |||||
ACT cases <10 years of age | 7 | 34 | 36 | 77 | ||||
Carriers without ACT | 730 | 1819 | 1536 | 4085 | ||||
Total | 737 | 1853 | 1572 | 4162 | ||||
ACT | ||||||||
Subregion | N | C.I. | Subregion | N | C.I. | RR | p Value | |
(/1000) | (/1000) | X2 | Fischer | |||||
C2 | 34 | 18.3 | C1 | 7 | 9.5 | 1.932 [0.86; 4.338] | 0.146 | 0.118 |
C3 | 36 | 22.9 | C2 | 34 | 18.3 | 1.248 [0.785; 1.985] | 0.414 | 0.397 |
C3 | 36 | 22.9 | C1 | 7 | 9.5 | 2.411 [1.078; 5.392] | 0.04 | 0.031 |
A | ||||
Subregion | ACT Cases <10 Years (2007–2018) | Persons <10 Years (2007–2018) | Incidence (<10 Years) /Million/Year | 95% CI |
C0 | 9 | 956,764 | 9.41 | 4.30; 17.86 |
C3 | 46 | 5,643,503 | 8.15 | 5.97; 10.87 |
C2 | 50 | 7,552,735 | 6.62 | 4.91; 8.73 |
C1 | 13 | 4,328,094 | 3.0 | 1.60; 5.14 |
B | ||||
Comparison | Incidence Rate Ratio (IRR) | 95% CI | Adjusted p (Bonferroni) | |
C0/C3 | 1.154 | 0.497; 2.386 | 1.0000 | |
C0/C2 | 1.421 | 0.614; 2.919 | 1.0000 | |
C0/C1 | 3.132 | 1.182; 7.919 | 0.0638 | |
C3/C2 | 1.231 | 0.807; 1.875 | 1.0000 | |
C3/C1 | 2.714 | 1.442; 5.475 | 0.0053 | |
C2/C1 | 2.204 | 1.180; 4.423 | 0.0514 |
A | |||||||
Code | Surveillance */Interval ** | Gender/ACC Age (Y) | Clinical Features | ACT Weight (g) | Stage/Treatment | Recurrence | Outcome/Present Age (Years) |
1 | Regular/4 months | F/6.2 | Acne | 14 | I/CR | No | Well/8.2 |
2 | Irregular/9 months | M/7.3 | Acne + pubic hair | 267 | II/CR + M | No | Well/11.4 |
3 | Irregular/22 months | F/5.8 | EnlargedClitoris, acne, pubic hair + H | NA | IV/PR + EDPM | Remained local tumor and metastases | DD/6.4 |
B | |||||||
Code | Surveillance */Interval ** | Gender/ACC Age (Y) | Clinical Features | ACT Weight (g) | Stage/Treatment | Recurrence | Outcome/Present Age (Years) |
1 | Regular/No PE | F/0.9 | Pubic hair | 21 | I/CR | No | Well/3.6 |
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Costa, T.E.J.; Gerber, V.K.Q.; Ibañez, H.C.; Melanda, V.S.; Parise, I.Z.S.; Watanabe, F.M.; Pianovski, M.A.D.; Fiori, C.M.C.M.; Fabro, A.L.M.R.; da Silva, D.B.; et al. Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil. Cancers 2019, 11, 1804. https://doi.org/10.3390/cancers11111804
Costa TEJ, Gerber VKQ, Ibañez HC, Melanda VS, Parise IZS, Watanabe FM, Pianovski MAD, Fiori CMCM, Fabro ALMR, da Silva DB, et al. Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil. Cancers. 2019; 11(11):1804. https://doi.org/10.3390/cancers11111804
Chicago/Turabian StyleCosta, Tatiana E. J., Viviane K. Q. Gerber, Humberto C. Ibañez, Viviane S. Melanda, Ivy Z. S. Parise, Flora M. Watanabe, Mara A. D. Pianovski, Carmem M. C. M. Fiori, Ana L. M. R. Fabro, Denise B. da Silva, and et al. 2019. "Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil" Cancers 11, no. 11: 1804. https://doi.org/10.3390/cancers11111804