Dear Sir,A recent review article in International Journal of Cancer underlined the role of tissue microenvironment in developmental regulation of tumor cells and showed that modifications of the stroma may revert tumor cells to a normal phenotype. 1 We present preliminary data suggesting that Down's Syndrome (DS) could be a natural model of cancer protection due to a particular cell microenvironment.An epidemiological study dealing with breast cancer in subjects with DS 2 and reports on cancer incidence 3-5 and death rates 6,7 in DS subjects have clearly showed a strikingly lower rate of breast neoplasms among DS subjects in comparison to non-DS subjects. If we consider the considerable increase in life expectancy among the DS population over the past 5 decades, breast neoplasms are estimated to be 10 -25 times less frequent in DS subjects than in the general population. 2,7 This makes DS, which is caused by a constitutional supernumerary chromosome 21 (trisomy 21), 8 the most powerful natural condition that offers protection against the most common malignant neoplasm in women, breast cancer. It is surprising that a genetic impairment may have such a favourable effect, but we believe that it deserves our undivided attention.From a broader oncological perspective, neoplasms in DS subjects have a very particular distribution pattern in comparison to those in the general population; this pattern is what we refer to as the "Down Syndrome tumour profile." 9 In DS subjects, some neoplasms are considerably or moderately overrepresented, some are represented at a similar frequency, whereas others are slightly or markedly under-represented, when compared to the non-DS population. One could therefore assume that the theoretical 1.5-fold overexpression of genes on chromosome 21 that characterises the DS condition has different positive, neutral and negative effects on tumour onset and progression, depending on the original tissue. Chromosome 21 is the smallest of our chromosomes, harbouring nearly 250 genes, which is just 1% of the human genome. 10 It is probable that some of the overexpressed genes resulting from the gene dosage effect and residing on the supernumerary chromosome 21 could have a protective or favourable effect on various tumour cells. To date, however, no single gene has been isolated to explain oncogenic events in DS.Another cause could be an epigenetic process at work due to the host microenvironment in persons with DS. On examining the features common to neoplasms that are rare or lacking in DS subjects, we were forced to seriously consider the role played by stroma. The stroma of a solid epithelial tumour consists of a population of non-malignant tumour cells including fibroblasts, and a main cell component, which produces the fibroblast extracellular matrix (ECM) surrounding the malignant cells. It is well established that the stroma plays a key role in malignant epithelial tumour homeostasis and development, 11 and it is particularly interesting that the most common malignancy in DS children and adu...
The purpose of this study was to assess the cytogenetic effects of the X ray irradiation used during a CT scan in order to estimate the mean absorbed dose in circulating lymphocytes. Chromosomal aberrations were scored in blood lymphocytes of ten patients undergoing CT scans, by applying fluorescence in situ hybridisation (FISH) to metaphase cells and premature chromosome condensation (PCC) with chromosomes 1, 3 and 4 painting probes immediately after exposure. This generated a dosimetric index that reflects the dose to the circulating lymphocytes. By using PCC a significant increase in the frequency of chromosomal fragment was observed immediately after a CT scan. However, no significant increase in chromosomal aberration was detected in metaphase cells. The mean dosimetric index immediately after exposure was 0.057 Gy (95% CI: 0.052-0.082 Gy). This dosimetric index depends essentially on the size of the examined and exposed blood volumes. This dose is in close agreement with the dose length product (DLP) (Gy cm) (R = 0.80). It should be kept in mind when justifying requests for diagnostic CT scan especially in young patients. The presence of chromosomal fragments after a CT scan indicated the cytogenetic effect of a low dose. PCC associated with chromosome painting is a method for detecting the cytogenetic effect of a low dose immediately after exposure.
Hoyeraal-Hreidarsson syndrome (HHS) is a severe infantile variant of X-linked dyskeratosis congenita (DC). The authors report evidence of increased in vitro sensitivity to radiation and alkylating agent in circulating lymphocytes and fibroblasts obtained from a 7-year-old boy with HHS. A major telomere shortening was also found (3 kb) as compared to healthy donors (10 kb). The standard treatments, chemotherapy regimens, and radiation therapy were not possible. The data suggest that conditioning regimens including TBI should not be used when a bone marrow transplantation procedure is planned in these patients.
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