Cancer Genetic Counseling (CGC) and genetic testing (GT) assume a paramount role for hereditary cancer predisposition syndrome families. We assessed the effects of CGC and GT on women affected by ...cancer who are at risk for hereditary breast and ovarian cancer predisposition syndrome (HBOC).
This study encompasses four time points: before the CGC session, after the CGC session when blood is drawn for GT, after disclosure of GT results, and six months following disclosure of GT results. The impacts of CGC and GT were assessed using psychosocial questionnaires. Additionally, a pedigree, genogram, and ecomap were constructed through a semistructured interview.
A total of sixty women were included in the study. Most participants considered their perception of cancer risk to be equivalent to that of the general population, even among those with pathogenic variants. An increased perception of breast and ovarian cancer risks was associated with a heightened inclination toward religious engagement as a coping mechanism. Patients carrying variants of uncertain significance expressed greater concerns about developing another cancer compared to those who had
and
wild type or pathogenic variants. Qualitative analysis of the genograms and ecomaps demonstrated that the CGC/GT processes facilitate communication within families. The genogram analyses revealed the impact of CGC and GT processes on families at risk for hereditary cancer. Changes in some family relationships were observed, and an improvement in communication was noted following the GT process.
These findings can assist healthcare professionals considering a personalized approaches in clinical practice.
Objective
There is a lack of information describing Brazilian women at risk of hereditary breast and ovarian cancer syndrome (HBOC) who undergo genetic cancer risk assessment (GCRA). This study aims ...to characterize the psychosocial profile of women at risk for HBOC at their first GCRA to obtain an overview of their families’ profiles and the challenges of the oncogenetics setting.
Methods
This was a cross‐sectional study in which interviews were conducted with 83 cancer‐affected women at their first GRCA appointment after the pedigree draw. Tools to evaluate psychological outcomes were applied. The pedigree genogram and ecomap were constructed and analyzed with content analysis using the “life course perspective” theory.
Results
Individuals perceived their breast/ovarian cancer risk to be equal to that of the general population, although they were highly concerned about developing cancer. No evidence of anxiety or depressive symptoms was identified. Participants used the coping strategy of searching for religiosity. The genograms and ecomaps resulted in five major themes: support and social support; attitudes, feelings and emotions; cancer causes; communication; and relationships with relatives. Individuals between 20‐29 years of age and those with no family history of cancer tended not to communicate with relatives, which may indicate future problems in the GCRA process regarding genetic testing.
Conclusions
This study demonstrated that knowing the families who undergo the GCRA process can help professionals provide more individualized and thorough attention during GCRA and genetic testing, which results in better follow‐up and prevention strategies.
The Brazilian TP53 mutation (R337H) and sarcomas Volc, Sahlua Miguel; Ramos, Cíntia Regina Niederauer; Galvão, Henrique de Campos Reis ...
PloS one,
01/2020, Volume:
15, Issue:
1
Journal Article
Peer reviewed
Open access
Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is ...central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.
In Brazil, the population in general has little knowledge about genetic risks, as well as regarding the role and importance of the Cancer Genetic Counseling (CGC). The goal of this study was to ...evaluate cancer-related worry and cancer risk perception during CGC sessions in Brazilian women at-risk for hereditary breast cancer. This study was performed in 264 individuals seeking CGC for hereditary breast cancer. Both cancer-affected and unaffected individuals were included. As results, individuals with and without cancer reported different motivations for seeking CGC and undergoing genetic testing. A correlation was observed between age at the first CGC session and age at which the closest relative was diagnosed with cancer. Multivariate analysis showed that educational level, cancer risk discussion within the family, and number of deaths by cancer among first-degree relatives influenced positively the cancer risk perception. In conclusion, the results of this study indicate that cancer-related worry and cancer risk perception are significant aspects of morbidity in individuals seeking CGC, whether they are cancer-affected or unaffected. CGC has an important role in health education and cancer prevention for its potential of promoting an accurate perception of the risk.
The use of gene panels introduces a new dilemma in the genetics field due to the high frequency of variants of uncertain significance (VUS). The objective of this study was to provide evidence that ...may help in the classification of these germline variants in terms of their clinical impact and association with the disease in question. A total of 52 unrelated women at-risk for HBOC and negative for
BRCA1/BRCA2
pathogenic variants were evaluated through a gene panel comprising 14 breast and/or ovarian cancer susceptibility genes. Of the 453 germline variants identified, 15 variants (classes 3, 4, and 5) in the
ATM, BRIP1, CHEK2, MRE11A, MUTHY, PALB2, RAD50
, and
RAD51C
genes were evaluated via databases, co-segregation studies and loss of heterozygosity in the tumor. The co-segregation analysis allowed the establishment of an association with the presence of variants and the risk of cancer for variant c.316C>T in the
BRIP1
gene. Four variants of uncertain significance showed loss of heterozygosity in the tumor (
ATM
c.4709T>C;
CHEK2
c.1036C>T;
PALB2
c.1001A>G, and
RAD50
c.281T>C), which is an indication of pathogenicity. Thus, the present study provides novel evidence that favors the association of variants in moderate-risk genes with the development of hereditary breast cancer.
Familial colorectal cancer type X (FCCTX) is a heterogeneous colorectal cancer predisposition syndrome that, although displays a cancer pattern similar to Lynch syndrome, is mismatch repair ...proficient and does not exhibit microsatellite instability. Besides, its genetic etiology remains to be elucidated. In this study we performed germline exome sequencing of 39 cancer-affected patients from 34 families at risk for FCCTX. Variant classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic/likely pathogenic variants were identified in 17.65% of the families. Rare and potentially pathogenic alterations were identified in known hereditary cancer genes (CHEK2), in putative FCCTX candidate genes (OGG1 and FAN1) and in other cancer-related genes such as ATR, ASXL1, PARK2, SLX4 and TREX1. This study provides novel important clues that can contribute to the understanding of FCCTX genetic basis.
Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, characterized by germline pathogenic variants in mismatch repair (MMR)-related genes that lead to microsatellite ...instability. Patients who meet the clinical criteria for LS and MMR deficiency and without any identified germline pathogenic variants are frequently considered to have Lynch-like syndrome (LLS). These patients have a higher risk of CRC and extracolonic tumors, and little is known about their underlying genetic causes. We investigated the germline spectrum of LLS patients through whole-exome sequencing (WES). A total of 20 unrelated patients with MMR deficiency who met the clinical criteria for LS and had no germline variant were subjected to germline WES. Variant classification was performed according to the American College of Medical Genetics and Genomics (ACMG) criteria. Pathogenic/likely pathogenic variants were identified in 35% of patients in known cancer genes such as MUTYH and ATM. Besides this, rare and potentially pathogenic variants were identified in the DNA repair gene POLN and other cancer-related genes such as PPARG, CTC1, DCC and ALPK1. Our study demonstrates the germline mutational status of LLS patients, a population at high risk of colorectal cancer.
This study evaluated the quality of life of 20 women with post-mastectomy lymphedema due to breast cancer, using the Flanagan’s Adapted Quality of Life Scale (1) and the Visual Analogue Scale (2), ...with data collection from July to December 2009 in the countryside of the state of São Paulo. It was observed a lower quality of life concerning participation in recreational and work activities, and better quality of life was related to relationship with friends; listening to music, reading, watching TV and going to the movies. Cronbach's alpha of Scale 1 was 0.86 and the average of Scale 2 was 6.26. Overall, the scales showed satisfactory results of quality of life, but low values showed factors that must be worked out, such as participation in sports, work and learning activities. Thus, lymphedema interferes with the quality of life, indicating a need for early intervention in order to help women achieve better quality of life.
The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole‐exome sequencing (WES) was performed in the germline DNA of 52 non‐BRCA1/BRCA2/TP53 mutation ...carrier women at high‐risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using information from population and disease specific databases, in silico prediction tools and the American College of Medical Genetics and Genomics (ACMG) criteria. Loss of heterozygosity (LOH) of tumor samples and segregation analyses were performed whenever possible. The variants identified were investigated in a second, independent cohort of 17 BC cases. Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as CHEK2, MUTYH, PMS2, and RAD51C. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer‐related genes such as DROSHA and SLC34A2. Interestingly, the variant c.149T>G in the FAN1 gene was identified in two unrelated families, and exhibited LOH in the tumor tissue of one of them. In conclusion, this is the largest Brazilian WES study involving families at high‐risk for HBOC which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.
The current study aimed to identify new breast and/or ovarian cancer predisposition genes. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer‐related genes such as DROSHA and SLC34A2. This is the largest Brazilian WES study involving families at high‐risk for hereditary breast and ovarian cancer which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.
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