Dataset Information

The Inherited p53 Mutation in the Brazilian Population.

ABSTRACT: A common criticism of studying rare diseases is the often-limited relevance of the findings to human health. Here, we review ?15 years of research into an unusual germline TP53 mutation (p.R337H) that began with its detection in children with adrenocortical carcinoma (ACC), a remarkably rare childhood cancer that is associated with poor prognosis. We have come to learn that the p.R337H mutation exists at a very high frequency in Southern and Southeastern Brazil, occurring in one of 375 individuals within a total population of ?100 million. Moreover, it has been determined that carriers of this founder mutation display variable tumor susceptibility, ranging from isolated cases of pediatric ACC to Li-Fraumeni or Li-Fraumeni-like (LFL) syndromes, thus representing a significant medical issue for this country. Studying the biochemical and molecular consequences of this mutation on p53 tumor-suppressor activity, as well as the putative additional genetic alterations that cooperate with this mutation, is advancing our understanding of how p53 functions in tumor suppression in general. These studies, which originated with a rare childhood tumor, are providing important information for guiding genetic counselors and physicians in treating their patients and are already providing clinical benefit.

SUBMITTER: Achatz MI

PROVIDER: S-EPMC5131754 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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The Inherited p53 Mutation in the Brazilian Population.

Achatz Maria Isabel MI Zambetti Gerard P GP

Cold Spring Harbor perspectives in medicine 20161201 12

A common criticism of studying rare diseases is the often-limited relevance of the findings to human health. Here, we review ∼15 years of research into an unusual germline TP53 mutation (p.R337H) that began with its detection in children with adrenocortical carcinoma (ACC), a remarkably rare childhood cancer that is associated with poor prognosis. We have come to learn that the p.R337H mutation exists at a very high frequency in Southern and Southeastern Brazil, occurring in one of 375 individua ...[more]

PMID: 27663983

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Project description:Colorectal cancer (CRC) is the third most common type of cancer among men and the second among women in Brazil. Despite the high incidence and significance of CRC in Brazil, very little is known about its prevalence among the asymptomatic population. Recently, a CRC screening program was implemented at the Cancer Hospital of Barretos. Characterization of the clinical findings detected in the screening population and the prevalence of basal CRC might contribute to better organization of the program and define the best strategy for a future national screening program. We hypothesize that recruitment and the early outcomes of our screening program based on the fecal immunochemical test (FIT) will differ from the outcomes corresponding to other populations due to sociodemographic differences. Aims: i. To implement a data collection and storage system for follow-up of the screening program participants and to measure early outcomes (adenoma, advanced adenoma and cancer) and associate them with sociodemographic risk factors; ii. to quantify the risk of CRC in the Brazilian population and to develop algorithms for risk stratification of CRC screening; and iii. to compare the risk stratification to other countries with low, medium and high incomes. Methods: Individuals aged 50 to 65 years will be included in the HCB screening program from November 2017 to December 2018. The following data will be collected from all participants: sociodemographic and ethnic (skin color) characteristics; risk factors for CRC, such as smoking and drinking; comorbidities, including diabetes mellitus and arterial hypertension; and FIT, colonoscopy and histopathology examination results. Data collection will be performed using the REDCap data collection/database system. The risk score will be formulated using the Chi-square test (or Fisher’s exact test) and simple logistic regression, and the regression coefficients will be calculated. Then, the model identified for the training sample will be replicated with a validation sample. The resulting score will be used to calculate the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, area under the receiver operating characteristic (ROC) curve and Kolmogorov D statistic.

Dataset Information

The Inherited p53 Mutation in the Brazilian Population.

Publications

The Inherited p53 Mutation in the Brazilian Population.

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