Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.
We identified 4316 unselected incident cases of early-onset breast cancers (<51 ears of age at diagnosis) in 18 Polish hospitals between 1996 and 2003. We were able to obtain a blood sample for DNA analysis from 3472 of these (80.4%). All cases were tested for the presence of three founder mutations in BRCA1. The proportion of cases with a BRCA1 mutation was 5.7%. The hereditary proportions were higher than this for women with breast cancer diagnosed before age 40 (9%), for women with cancer of medullary or atypical medullary histology (28%), for those with bilateral cancer (29%) or with a family history of breast or ovarian cancer (13%). It is reasonable to offer genetic testing to women with early-onset breast cancer in Poland.
Entosis is a phenomenon, in which one cell enters a second one. New clinico-histopathological studies of entosis prompted us to summarize its significance in cancer. It appears that entosis might be a novel, independent prognostic predictor factor in cancer histopathology. We briefly discuss the biological basis of entosis, followed by a summary of published clinico-histopathological studies on entosis significance in cancer prognosis. The correlation of entosis with cancer prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma and breast ductal carcinoma, is shown. Numerous entotic figures are associated with a more malignant cancer phenotype and poor prognosis in many cancers. We also showed that some anticancer drugs could induce entosis in cell culture, even as an escape mechanism. Thus, entosis is likely beneficial for survival of malignant cells, i.e., an entotic cell can hide from unfavourable factors in another cell and subsequently leave the host cell remaining intact, leading to failure in therapy or cancer recurrence. Finally, we highlight the potential relationship of cell adhesion with entosis in vitro, based on the model of the BxPc3 cells cultured in full adhesive conditions, comparing them to a commonly used MCF7 semiadhesive model of entosis.
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