Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sun exposure histories were obtained from a series of patients age 35 or younger following diagnosis and removal of a basal cell carcinoma (BCC). The DNA was extracted from tumor biopsy samples derived from BCC of 10 patients who reported that they did not use sunscreens during youth (age 18 or younger) and 10 patients who routinely employed sunscreens during this age period. Exons 5-9 of the p53 gene were then amplified in three fragments from these samples using a nested polymerase chain reaction (PCR) approach and screened for mutations using an RNA heteroduplex assay. All PCR products displaying evidence of a mutation were sequenced. It was found that 6 of the 10 patients who were not routine sunscreen users displayed mutations in these p53 exons. All of the mutations were located at dipyrimidine sites, five of the six were C-->T transitions and one mutation was a tandem double mutation, consistent with a role for solar UVB in BCC formation. In contrast, only one p53 mutation was detected in the group of 10 patients who routinely employed sunscreens during childhood and adolescence. Hence, a significantly (P = 0.029) lower level of p53 mutations was detected in the BCC obtained from sunscreen users compared with tumors derived from nonusers. These findings suggest that the mechanisms involved in the etiology of skin carcinogenesis differ in sunscreen users compared with people who did not routinely employ sunscreens. These data are also indicative of a protective effect associated with sunscreen use against the formation of p53 mutations. It is possible that the patients who were diagnosed with BCC despite their use of sunscreens possessed a genetic susceptibility for skin cancer formation and developed BCC through a p53-independent pathway. Alternatively, solar UVA wavelengths, that were generally not blocked by the suncare products employed by the sunscreen users, may have played a significant role in BCC development through induction of a mutation(s) in an oncogene and/or a tumor suppressor gene, other than p53, for these patients.
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PMID:p53 mutations in basal cell carcinomas arising in routine users of sunscreens. 1056 72

Although basal cell carcinoma (BCC) is a major skin cancer, the mechanism of carcinogenesis with regard to cytogenetic abnormalities has not been fully investigated. In the present study, we carried out cytogenetic analyses of 18 patients (9 male and 9 female) with BCC. Aneuploidy was seen by Q-banding method in more than half of the cases and was mostly loss of the sex chromosome. We also performed FISH to the interphase nuclei of various tissues and short-term cultured BCC cells. The frequency of sex chromosomal aneuploidy was significantly higher in all samples from BCC patients (peripheral blood lymphocytes, non-lesional tissues, BCC tumor tissues and cultured BCC cells) than in age-matched normal controls. In addition, we analyzed clonality of BCC tissues using a human androgen receptor gene assay and found uniparental pattern of inactive X-chromosomes. This indicates that BCC cells were monoclonal in origin and the development of BCC might be correlated with sex chromosomal aneuploidy, which acquired accumulation of genetic mutations.
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PMID:Aneuploidy of sex chromosomes in basal cell carcinoma: its clonality and involvement in the development of carcinogenesis. 1060 43

In this retrospective, nation-wide cohort study, the risk of cancer was assessed for 1738 Danish patients with psoriasis subjected to climatotherapy at the Dead Sea during 1972-93, by linkage to the Danish Cancer Registry. The overall risk of cancer in patients treated at the Dead Sea (standardized incidence ratio, SIR = 1.59) was higher than that expected in the general population, owing to an excess risk of non-melanoma skin cancer (NMSC) [SIR = 4.2 for basal cell carcinoma (BCC) and 10.7 for squamous cell carcinoma (SCC)]. In addition, the distribution of NMSC among body sites, age groups and sexes was unusual in those treated at the Dead Sea, favouring NMSC in young individuals and at multiple sites (SIR = 10.7 for BCC and 57.2 for SCC), multiple BCCs being particularly common among young women. Thus, people subjected to climatotherapy at the Dead Sea for psoriasis constitute a high-risk group for NMSC, SCC in particular, but not for malignant diseases in general. The study design precludes conclusions on whether climatotherapy plays a specific part in skin carcinogenesis which is different from other sources of ultraviolet (UV) radiation, as climatotherapy is inevitably confounded by excess UV exposure.
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PMID:Malignant tumours and psoriasis: climatotherapy at the Dead Sea. 1116 17

While ultraviolet (UV) exposure is thought to be a major risk factor for basal cell carcinoma (BCC) and squamous cell carcinoma, more recent research has focused on genetic factors predisposing to these cancers. UV constitutes an oxidative stress with generation of free radicals, leading to lipid and DNA damage and gene mutation. It could therefore be hypothesized that individual ability to deal with these products may be important in cutaneous carcinogenesis. It is clear from recent studies that polymorphisms in detoxifying enzyme genes are important in determining susceptibility to skin cancer. The magnitude of effect in BCC is similar to that seen with many other previously described risk factors. However, uncertainties exist regarding the phenotypic consequences of some of these polymorphisms and relevant substrates. This review describes the influence of polymorphisms in detoxifying enzymes in determining susceptibility to skin cancer (in particular to BCC) and give a brief overview of the biochemistry of the detoxification process.
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PMID:Detoxifying enzyme genotypes and susceptibility to cutaneous malignancy. 1065 88

Basal cell carcinoma (BCC) is the most common type of human cancer, often locally invasive, and following a benign clinical course. However, a proportion of BCCs do recur after treatment, causing extensive local tissue destruction, seldom metastasizing. Morphological methods to unequivocally distinguish the aggressive forms of these tumors (BCC2) from the ordinary ones (BCC1) have so far been lacking. Apoptosis, or programmed cell death, is thought to be important for the death of tumor cells in various stages of carcinogenesis. We analyzed the extent of apoptosis in BCCs of head and neck in a morphological, morphometric, and electron-microscopic study, to estabilish on a retrospective basis, the relative frequency of recurrence of tumors showing different apoptotic rates. We found that BCC1 showed lower apoptotic index (AI) than BCC2 [BCC1: AI from 2.03 to 10.45% (mean value: 5.98%) BCC2: AI from 21. 91 up to 43.82% (mean value: 39.82%)]. The morphometric analysis of both BCC1 and BCC2 revealed significant differences between the values concerning nuclear area, length, perimeter, and roundness of the apoptotic cells with respect to the 'viable' neoplastic cells. Electron-microscopy confirmed that the features of morphological apoptotic cells were characteristic of programmed cell death. We hypothesized that low apoptotic rates in BCC1 could be indicative of a good prognosis. In fact, this corresponded to an 'expansive' but not still invasive neoplastic state. In this phase, however, the tumor cells may constitute the target for genetic changes triggered by enviromental physical or chemical mutagenic agents, such as UV rays. BCC2, then, could be the result of newly selected mutated neoplastic cellular clones, with more aggressive biological behavior. The high apoptotic level found in BCC2 could thus be used as an indirect alarm signal from pathologists. This hypothesis seems to be supported by most of the current data in the literature and by the clinical outcome of BCC2 of our series. In our opinion, routine evaluation of apoptosis in BCCs could be proposed to facilitate their sub-classification, contributing toward the evaluation of the prospective outcome of the individual patients.
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PMID:Prognostic value of apoptotic index in cutaneous basal cell carcinomas of head and neck. 1070 87

Skin cancer is the most commonly occurring cancer in humans. Solar keratoses are related benign tumours that are at least ten times commoner than skin cancers and photoageing of the skin is still more common. Descriptive studies show that incidence rates of the main types of skin cancer, basal cell carcinoma, squamous cell carcinoma and melanoma are maximal in populations in which ambient sun exposure is high and skin (epidermal) transmission of solar radiation is high, suggesting strong associations with sun exposure. Analytic epidemiological studies confirm that exposure to the UV component of sunlight is the major environmental determinant of skin cancers and associated skin conditions and evidence of a causal association between cumulative sun exposure and SCC, solar keratoses and photodamage is relatively straightforward. Results for BCC and melanoma are complicated by several factors including the existence of subgroups of these diseases which do not appear to be caused by sun exposure yet have been included in most aetiological studies to date. Complementary to epidemiological data is the molecular evidence of ultraviolet (UV) mechanisms of carcinogenesis such as UV-specific mutations in the DNA of tumour suppressor genes in skin tumours. With increased UV irradiation resulting from thinning of the ozone layer, skin cancer incidence rates have been predicted to increase in the future--unless, as is hoped, human behaviour to reduce sun exposure can offset these predicted rises.
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PMID:Sun exposure, skin cancers and related skin conditions. 1070 45

Although the overexpression of cyclin D1 has been believed to play important roles in neoplastic transformation of some tumors, little is known about the function of cyclin D1 protein in carcinogenesis in human skin. A total of 307 patients with nonmelanocytic skin cancer, being 46 with Bowen's disease (BOD), 134 with squamous cell carcinoma (SCC) and 127 with basal cell carcinoma (BCC), were investigated immunohistochemically using monoclonal antibody to cyclin D1 by the LSAB method, to assess the expression of cyclin D1 in skin cancer including its precursors. The positive rates of cyclin D1 immunostaining in BOD, SCC and BCC were 63.0%, 69.4% and 54.3%, respectively. The positive rates in dysplasia adjoining BOD, SCC and BCC were 43.6%, 67.9% and 59.8%, respectively. In morphologically normal skin, however, only 2 cases, 1 of SCC and 1 of BCC, exhibited positive staining. These findings suggested that overexpression of cyclin D1 is an early event in dysplastic lesions of skin. Overexpression of cyclin D1 was related to sun exposure, especially in dysplasia of SCC. The score for cyclin D1 expression in dysplasia of BCC was correlated with age. Expression of cyclin D1 markedly increased from normal skin through dysplasia to BOD, but was not significantly related to the degree of SCC differentiation. These findings demonstrate that the effect of cyclin D1 overexpression is restricted to proliferation of cells, so that they gain a growth advantage, but their differentiation is not increased. Comparison with the results for p53 protein expression in these tumors, a significant correlation with cyclin D1 expression was found in dysplasia in BOD and SCC, and in patients with BCC who were less than 74 years old. These findings suggested the hypothesis that prior aberrant p53 expression may affect or regulate the overexpression of cyclin D1.
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PMID:Overexpression of cyclin D1 in nonmelanocytic skin cancer. 1083 41

Nonmelanoma skin cancers (NMSC) has been evidenced with an impaired function in nucleotide excision repair (NER). However, malfunction of NER elements in NMSC has not been identified. Xeroderma pigmentosum F (XPF) is an essential subunit in NER and functions as a 5'-incision enzyme when repairing damaged DNA. So far, neither XPF's protein nor antibody is commercially available. To explore the expression of XPF in NMSC, the gene was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR). All the designed primers specifically amplified XPF cDNA as demonstrated by nested PCR, and one set of the primers was mimic constructed to form a controlled cDNA for the semiquantification of XPF gene in NMSC. The results indicated that the quantities of XPF expression of BCC and SCC specimens were approximately 57.0 and 76.4% less than that of normal skins, respectively. This paper indicates that the decrease expression of XPF gene may be one of mechanisms for impaired NER in NMSC, and the feasible and quantitative primers used in the experiments may explore the study of XPF in etiology of carcinogenesis.
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PMID:Quantitative determination of the expression of xeroderma pigmentosum F gene in human nonmelanoma skin cancers. 1087 27

DNA of human papillomaviruses has frequently been detected in nonmelanoma skin cancers, raising the question of a possible causal contribution of these tumor viruses to skin carcinogenesis. Basal cell carcinomas are the most common nonmelanoma skin cancers; however, so far they are only poorly analyzed with regard to human papillomavirus infection. We searched for human papillomavirus-DNA in 69 biopsies from 61 immunocompetent basal cell carcinoma patients from two geographic locations in Europe using six different polymerase chain reaction primer systems. We could demonstrate human papillomavirus-DNA in 43.5% of the tested tumors. Human papillomavirus positivity did not seem to correlate with the duration of disease or patients' age. The vast majority of virus types in the biopsies belonged to the group of epidermodysplasia verruciformis-associated human papillomavirus. Of 31 sample pairs tested for human papillomavirus-DNA in tumors as well as in perilesional healthy skin, seven carried viral sequences in lesional and healthy skin and three only in the basal cell carcinoma. Six of the seven human papillomavirus-positive basal cell carcinoma/healthy skin pairs contained identical human papillomavirus types in tumors and histologically normal tissue. Forty basal cell carcinoma patients were additionally analyzed for IgG antibodies against virus-like particles of three representative epidermodysplasia verruciformis-human papillomavirus types: 8, 15, and 36. No statistically significant differences could be detected between human papillomavirus antibody prevalences of basal cell carcinoma patients and of dermatologically healthy individuals. Moreover, serologic findings did not correlate with the detection of specific human papillomavirus types in tumors. Our results seem to suggest that the occurrence of human papillomavirus-DNA in basal cell carcinoma does not reflect a major etiologic role of human papillomavirus in this cancer.
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PMID:Communication: papillomavirus DNA in basal cell carcinomas of immunocompetent patients: an accidental association?TITLE. 1088 19

Several studies have shown that the presence of genetic instability can be associated to carcinogenesis process. The detection of microsatellite instability (MI) that consists of an expansion and/or deletion of DNA within repeat sequences, may constitute a sensitive marker for the presence of gene mutations. A series of 18 basal cell carcinoma (BCC) consecutive patients was examined for the presence of alteration in 12 DNA microsatellite markers, in order to better understand the molecular significance of MI in the genesis and progression of BCC. Molecular alterations were detected in 6 out of 12 analyzed microsatellite loci. Five out of 18 BCC samples showed loss of heterozygosity at chromosome loci localized in the vicinity of the tumor suppressor genes, whereas six out of 18 BCC patients presented at least one altered microsatellite (instability). We demonstrated molecular genetic alterations at 2p16 locus, in the proximity of MSH2 <mismatch repair> gene and 17p21, in the proximity of the p53 gene. These data validate and confirm a role of MI in genesis and progression of BCC, by analysis of markers localized at specific chromosome region in proximity of oncogenes and tumor suppressor genes.
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PMID:Molecular detection of microsatellite instability in basal cell carcinoma. 1094 49


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