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. 2019 Nov 16;11(11):1804.
doi: 10.3390/cancers11111804.

Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil

Tatiana E J Costa  1   2   3 , Viviane K Q Gerber  1   4 , Humberto C Ibañez  1 , Viviane S Melanda  5 , Ivy Z S Parise  1   2   3 , Flora M Watanabe  6 , Mara A D Pianovski  7 , Carmem M C M Fiori  8 , Ana L M R Fabro  2   6 , Denise B da Silva  3 , Diancarlos P Andrade  1   2 , Heloisa Komechen  1   9 , Monalisa C Mendes  1   9 , Edna Carboni  6 , Ana Paula Kuczynski  6 , Emanuelle N Souza  1   9 , Mariana M Paraizo  1   2   9 , Marilea V C Ibañez  1 , Laura M Castilho  9 , Amanda F Cruz  9 , Thuila F da Maia  9 , Cleber Machado-Souza  1   2 , Roberto Rosati  1   2 , Claudia S Oliveira  1   2 , Guilherme A Parise  9 , Jaqueline D C Passos  9 , José R S Barbosa  1   9 , Mirna M O Figueiredo  9 , Leniza Lima  7   10 , Tiago Tormen  7   10 , Cesar C Sabbaga  6 , Sylvio G A Ávilla  6 , Leila Grisa  6 , Airton Aranha  6 , Karina C F Tosin  9 , Karin R P Ogradowski  1   2 , Geneci Lima  1 , Edith F Legal  2 , Tania H Anegawa  11   12 , Tânia L Mazzuco  13 , André L Grion  1 , José H G Balbinotti  1 , Karin L Dammski  1 , Rosiane G Melo  1   2 , Nilton Kiesel Filho  6 , Gislaine Custódio  9 , Bonald C Figueiredo  1   2   9   14
Affiliations

Penetrance of the TP53 R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil

Tatiana E J Costa et al. Cancers (Basel). .

Abstract

The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates.

Keywords: Li–Fraumeni syndrome; R337H; TP53; adrenocortical carcinoma; children; environmental modifiers.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) R337H frequencies among newborns from 22 Paraná Administrative Health Regions (AHRs) and (B) from 16 Santa Catarina AHRs (stored blood collected in 2013–2014). AHRs are represented by bold italic numbers.
Figure 2
Figure 2
The R337H frequencies (population versus ACT) and the obtained linear regression (LR) based on the overall averages for each state (SP, Paraná state (PR), and Santa Catarina (SC)). The blue straight line was obtained by simple LR using the method of least squares weighted by the number of individuals tested in each state, assuming equal weights for the considered variables. The shaded area represents the 95% confidence interval of the line assuming the normality of the errors.
Figure 3
Figure 3
ACT-free probability in the 2006-C cohort.
See this image and copyright information in PMC

References

    1. National Cancer Institute . In: SEER Cancer Statistics Review, 1975–2007. Altekruse D.F., Kosary C.L., Krapcho M., Neyman N., Aminou R., Waldron W., Ruhl J., Howlader N., Tatalovich Z., Cho H., et al., editors. National Cancer Institute; Bethesda, MD, USA: 2010.
    1. Bernstein L., Gurney J.G. Carcinomas and other malignant epithelial neoplasms. In: Ries L.A.G., Smith M.A., Gurney J.G., Liney M., Tamra T., Young J.L., Bunin G.R., editors. Cancer Incidence and Survival among Children and Adolescents: United States Seer Program 1975–1995. National Cancer Institute, SEER Program; Bethesda, MD, USA: 1999. pp. 139–147.
    1. Custódio G., Parise G.A., Kiesel Filho N., Komechen H., Sabbaga C.C., Rosati R., Grisa L., Parise I.Z., Pianovski M.A., Fiori C.M., et al. Impact of neonatal screening and surveillance for the TP53 R337H mutation on early detection of childhood adrenocortical tumors. J. Clin. Oncol. 2013;31:2619–2626. doi: 10.1200/JCO.2012.46.3711. - DOI - PMC - PubMed
    1. IARC Scientific Publication . In: International Incidence of Childhood Cancer. Parkin D.M., Kramarova E., Draper G.J., Masuyer E., Michaelis J., Neglia J., Qureshi S., Stiller C.A., editors. Volume 2 IARC Scientific Publication; Lyon, France: 1998.
    1. Stiller C.A. International variations in the incidence of childhood carcinomas. Cancer Epidemiol. Biomark. Prev. 1994;3:305–310. - PubMed