[Malignant mesothelioma risk factors: experience in the General Hospital of Mexico]. / Mesotelioma maligno: factores de riesgo, experiencia en el Hospital General de México.

BACKGROUND: Malignant mesothelioma is a neoplasm of bad prognosis, it is linked with asbestos contact, but there are cases without this antecedent. OBJECTIVE: To investigate the relationship of asbestos exposition and other factors with malignant mesothelioma. METHODS: Retrospective analysis of histologic confirmed cases of malignant mesothelioma, neoplasic familiar history, tobacco smoking, exposure to wood smoke and to asbestos, were annotated in a paired case/control study 1: 1-3 with logistic regression model to identify risk factors for OR. RESULTS: 61 cases of malignant mesothelioma were confirmed by histopathologic study, 41 male and 20 female. Mean age was 56 years ± 13 years; 56 cases (91.8%) correspond to epithelial malignant mesothelioma, three sarcomatous (4.9%) one desmoplastic and one biphasic. One in eight (13.1%) had exposure to asbestos. Model of logistic regression with four variables: history of familiar cancer, tobacco smoking, wood smoke and asbestos exposition, the the last one with an OR= 3.083 and p > 0.05. No other variables found to be a risk factor for malignant mesothelioma. CONCLUSIONS: Exposure to asbestos is a risk factor for malignant mesothelioma, which is confirmed in this study, however it is important to extend the investigation of other possible causal factors of this disease.

Antecedentes: el mesotelioma maligno es un tumor de mal pronóstico relacionado con el contacto con asbesto; sin embargo, existen numerosos casos sin este antecedente. Objetivo: describir la relación entre la exposición al asbesto y otros factores con el mesotelioma maligno. Material y métodos: estudio retrospectivo de casos y controles pareado 1: 1-3 por edad y sexo de pacientes con diagnóstico de mesotelioma maligno. Se registraron: la exposición al asbesto, tabaco, humo de leña y antecedentes familiares de cáncer. Se empleó regresión logística para razones de momios (ORs). Resultados: se estudiaron 61 casos con mesotelioma maligno, 41 hombres y 20 mujeres. La edad promedio fue 56 ± 13 años; 56 casos fueron mesotelioma maligno epitelial (91.8%), tres sarcomatosos (4.9%), uno desmoplásico y uno bifásico. Sólo en 8 (13.1%) se identificó exposición al asbesto. En el modelo de regresión logística el asbesto tuvo una razón de momios de 3.083 p > 0.05. Ninguna otra variable resultó ser un factor de riesgo para mesotelioma maligno. Conclusiones: la exposición al asbesto es un factor de riesgo para mesotelioma maligno, lo que se confirma en este estudio; sin embargo, es importante ampliar la investigación de otros posibles factores causales de esta enfermedad.

Genetics of breast cancer: Applications to the Mexican population

Breast cancer research has yielded several important results including the strong susceptibility genes,BRCA1 and BRCA2 and more recently 19 genes and genetic loci that confer a more moderate risk.The pace of discovery is accelerating as genetic technology and computational methods improve. These discoveries will change the way that breast cancer risk is understood in Mexico over the next few decades.

La investigación en cáncer de mama ha dado varios resultados importantes incluyendo los genes fuertemente susceptibles, BRCA1 y BRCA2, y más recientemente 19 genes y loci genéticos que confieren un riesgo moderado. El ritmo de los descubrimientos se acelera conforme mejora la tecnología y métodos computacionales.Estosdescubrimientoscambiarán la forma en que la investigación del cáncer es comprendida en México en las próximas décadas.

Predisposición genética para el cáncer de mama: genes BRCA1 y BRCA2 / Genetic predisposition for breast cancer: BRCA1 and BRCA2 genes

El descubrimiento de los genes BRCA1 y BRCA2 ha llevado a la introducción de pruebas genéticas cada vez más sofisticadas para medir el riesgo de cáncer de mama de origen hereditario, entre otras cosas. En el presente artículo exploramos los criterios a seguir para realizar pruebas para estos genes, así como las implicaciones en el tratamiento para los pacientes en caso de identificarlos.

The discovery of genes BRCA1 and BRCA2 has led to the introduction of genetic tests more complex every time for the evaluation ofthehereditarycancerrisk,amongothers.In the present paper we explore the criteria to decide when to run the testing for the genes, as well as the implications for the treatment of patients who are identified with them.

Genetics of breast cancer: applications to the Mexican population.

Breast cancer research has yielded several important results including the strong susceptibility genes,BRCA1 and BRCA2 and more recently 19 genes and genetic loci that confer a more moderate risk.The pace of discovery is accelerating as genetic technology and computational methods improve. These discoveries will change the way that breast cancer risk is understood in Mexico over the next few decades.

[Genetic predisposition for breast cancer: BRCA1 and BRCA2 genes]. / Predisposición genética para el cáncer de mama: genes BRCA1 y BRCA2.

The discovery of genes BRCA1 and BRCA2 has led to the introduction of genetic tests more complex every time for the evaluation of the hereditary cancer risk, among others. In the present paper we explore the criteria to decide when to run the testing for the genes, as well as the implications for the treatment of patients who are identified with them.

Neoplasia in familial dysautonomia: a 20-year review in a young patient population.

We reviewed the charts of all patients with familial dysautonomia (n = 631) and found that 2% had been diagnosed with tumors. We hypothesize that the IkappaB Kinase-associated protein gene mutation, which causes aberrant RNA splicing in patients with familial dysautonomia, may contribute to tumorigenesis in this genetically homogenous patient population.

High frequency of loss of heterozygosity at 11p15 and IGF2 overexpression are not related to clinical outcome in childhood adrenocortical tumors positive for the R337H TP53 mutation.

A germline TP53 R337H mutation is present in childhood adrenocortical tumors (ACT) from southern Brazil. Other genetic alterations are also frequently found in these tumors. This study was designed to assess whether alterations of the 11p15 region exist in childhood ACT, accounting for IGF2 overexpression in these tumors, and how they are related to clinical outcome. Tumor DNA of 12 children with ACT (4 adenomas and 8 carcinomas) and from the blood of their parents was analyzed. All patients showed 11p15 loss of heterozygosity (LOH) in the tumor. In contrast to the single case of paternal LOH, IGF2 was overexpressed in tumors with maternal allele loss. Our data show that 11p15 LOH is a widespread finding in childhood ACT not related with malignancy, contrary to adult ACT. Alterations in the expression of other genes in the same region (e.g., CDKN1C) may contribute to ACT tumorigenesis.

Family history of cancer in Brazil: is it being used?

In developing countries, low budgets make the issue of integrating genetics into clinical practice a challenge, a situation in which the use of family history (FH) becomes important for patient care, as it is a low cost strategy and a risk assessment tool. The purpose of this study was to review medical records of patients with colorectal cancer (CRC) seen in a public University Hospital and evaluate how often FH of cancer is registered. Initially we searched a database for patients who were seen in our hospital between 2002 and 2004 with the diagnosis of CRC. We found 415 patients, 104 of whom were excluded. A total of 311 charts were reviewed and classified into 3 groups. Group A: no FH documented; group B: FH was documented, but FH of cancer was not collected; and group C: FH of cancer was documented. We also investigated what type of information was recorded, in order to verify if important elements were assessed. Ninety-eight charts (31.5%) were classified in group A, 20 (6.5%) in group B, and 193 (62%) in group C. In addition, we observed that important information regarding affected relatives was not collected in most of the charts. In conclusion, we found that although FH of cancer was recorded in 62% of charts of patients with CRC, information that could be relevant for risk assessment and management of at-risk families was missing. Our findings expose an important problem in health education that could reflect negatively in the quality of medical assistance to individuals at risk for familial cancer.

Clinical characterization and risk profile of individuals seeking genetic counseling for hereditary breast cancer in Brazil.

Hereditary breast cancer (HBC) accounts for 5-10% of breast cancer cases and it significantly increases the lifetime risk of cancer. Our objective was to evaluate the sociodemographic variables, family history of cancer, breast cancer (BC) screening practices and the risk profile of cancer affected or asymptomatic at-risk women that undergo genetic counseling for hereditary breast cancer in public Brazilian cancer genetics services. Estimated lifetime risk of BC was calculated for asymptomatic women using the Gail and Claus models. The majority of women showed a moderate lifetime risk of developing BC, with an average risk of 19.7% and 19.9% by the Gail and Claus models, respectively. The average prior probability of carrying a BRCA1/2 gene mutation was 16.7% and overall only 32% fulfilled criteria for a hereditary breast cancer syndrome as assessed by family history. We conclude that a significant number of individuals at high-risk for HBC syndromes may not have access to the benefits of cancer genetic counseling in these centers. Contributing factors may include insufficient training of healthcare professionals, disinformation of cancer patients; difficult access to genetic testing and/or resistance in seeking such services. The identification and understanding of these barriers is essential to develop specific strategies to effectively achieve cancer risk reduction in this and other countries were clinical cancer genetics is not yet fully established.

Molecular biology in colorectal cancer.

Cancer is a genetic disease. Colorectal cancer is probably the type of cancer for which the most is known about the genes affected by cancer-causing mutations, their normal functions and their carcinogenic effects when mutated. Most cancer-causing mutations are somatic, occurring in the affected tissue during the course of carcinogenesis. However, most cancers also have a hereditary component that is caused by predisposing mutations that affect the germline, are heritable and contribute to the initiation of carcinogenesis. High-penetrance mutations confer predisposition to colorectal cancer mainly in Lynch syndrome (which involves mutations in mismatch-repair genes) and in familial adenomatous polyposis (which involves mutations in the APC tumour suppressor). Together, these conditions account for 5% or less of all cases of colorectal cancer. Low-penetrance mutations account for a high proportion of all the attributable risk of colorectal cancer, in both familial and sporadic cases. These mutations are more difficult to identify, but mainly due to the implementation of association studies, are increasingly being detected and characterized. The identification of both high- and low-penetrance mutations contributes significantly to our understanding of the molecular genetic processes occurring in cancer. This understanding facilitates the development of therapeutic drugs and preventive strategies.

Adenomatous polyposis coli gene as a gatekeeper.

The Adenomatous Polyposis Coli (APC) Gene is a tumor suppressor gene located in the chromosome 5q21. It has a sequence of 2843 amino acids and a weight of 312 kD. The mutation of the APC gene occurs at the early stages of most sporadic colorectal cancers; and up to 30% in familial adenomatous polyposis. The absence of APC will indicate the inadequate migration of colon mucous cells and its accumulation resulting in polyps formation, which determines a stage in carcinogenicity. An adequate study in prone groups may lead to chemoprophylaxis and/or early treatment of polyps.

[Global analysis strategies. Toward the genetic management of neoplasias]. / Estrategias de análisis global. Hacia el manejo genético de las neoplasias.

Biomedical research in oncological diseases, particularly focused on the study and understanding of the molecular mechanisms involved in cellular transformation, is opening new possibilities for the development of new and more efficient strategies for diagnosis and treatment. The generation and practical application of the results derived from molecular genetic studies in cancer, has evolved in parallel with the development of technological tools that allow us to get a global vision of diverse cellular processes, both in the normal and pathological states. This combination of basic research and technological application, has created methodologies that allow us to analyze the three principal levels of Molecular Genetics, the Genome (DNA, archive of the genetic information), the Transcriptome (RNA, expression of the genetic information), and finally, the Proteome (proteins, functional aspect of the genetic information). The vast amount of information obtained due to these advancements has begun to modify our fundamental vision about oncological diseases, and together with the traditional analytic tools, they hold the promise of changing the ways we classify, detect, diagnose and treat cancer. In this review, we present some of this methods for global genetic analysis, involving the three levels of genetic organization: the genome, with the Human Genome Project, comparative genomic hybridization and chromosome painting; the Transcriptome, with Serial analysis of Gene Expression and DNA microarrays; and the proteome, with bidimensional protein electrophoresis and antibody-microarrays. In each case, together with a brief description of the method, we also present the impact of every one of them on the study and management of neoplastic diseases.