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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The following conclusions are derived from an epidemiological study. Reduced repair of ultraviolet (UV)-induced DNA damage contributes directly to basal cell carcinoma (BCC) in individuals with prior sunlight overexposure. A family history of BCC is a predictor of low DNA repair. Repair of UV-damaged DNA declines at a fixed rate of approximately 1% per annum in noncancerous controls. The DNA repair differences between young BCC cases and their controls disappear as they age. Hence, BCC, in terms of DNA repair, is a premature aging disease. The persistence of photochemical damage because of reduced repair results in point mutations in the p53 gene and allelic loss of the nevoid BCC gene (Gorlin's syndrome) located on chromosome 9q. The fact that environmental vulnerability is gender oriented implicates hormones in regulating DNA repair. Xeroderma pigmentosum appears to be a valid paradigm for the role of DNA repair in BCC in the general population.
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PMID:Epidemiology of ultraviolet-DNA repair capacity and human cancer. 925 82

The MSSE gene predisposes to the development of multiple invasive but self-healing skin tumours (multiple self-healing squamous epitheliomata, MSSE). MSSE (previously named ESS1) was mapped to chromosome 9q by linkage analysis; haplotype analysis in families then suggested a common founder mutation and indicated that the gene lies in the interval D9S1-D9S29 (9q22-q31). Squamous cell carcinomata also develop as one of the complications of xeroderma pigmentosum, and one of the xeroderma pigmentosum genes (XPA) maps within the MSSE interval. We have investigated the hypothesis that a novel dominant mutation in XPA is responsible for MSSE. We screened the entire coding region, 3' untranslated region (UTR) and 5'UTR of XPA for germline mutations in MSSE families by single-stranded conformation polymorphism analysis and by direct DNA sequencing. No mutations were detected but a novel intragenic polymorphism was identified in the 5'UTR of XPA, in both MSSE-affected and unrelated normal individuals. This XPA polymorphism and nine new polymorphic markers that map in the MSSE region were typed in eleven MSSE families; XPA was excluded as the MSSE gene and the most likely location of MSSE was reduced to the interval between D9S197 and (D9S287, D9S1809). The Patched (PTCH) gene, which is mutated in naevoid basal cell carcinoma syndrome (NBCCS or Gorlin syndrome) lies in this interval and all MSSE families have been shown to share a common haplotype at three novel intragenic PTCH polymorphisms. Although no mutation has been detected in MSSE families, PTCH has not been excluded as the MSSE gene.
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PMID:Mapping the multiple self-healing squamous epithelioma (MSSE) gene and investigation of xeroderma pigmentosum group A (XPA) and PATCHED (PTCH) as candidate genes. 943 61

Basal cell carcinoma is the most common of all skin cancers and the most prevalent one among Caucasians. Rarely, these tumors are seen in other races. We report a 77-year-old Korean woman who presented with multiple darkly pigmented enlarging nodules on her scalp, face, trunk, and extremities. The patient had first noted a 6-mm pigmented lesion on her left eyebrow 10 years previously. Since then, other lesions had appeared in many locations on her body. She had been otherwise healthy and without a history of exposure to arsenic or radiation. There was no family history of skin cancer, xeroderma pigmentosum, or basal cell nevus syndrome. On physical examination, multiple darkly pigmented dome-shaped papules and nodules were present on her scalp, face, right forearm, lower abdomen, and inguinal areas. They ranged in size from 0.5 mm to 2 cm. The larger ones showed central ulceration. Multiple biopsy specimens from different sites showed pigmented basal cell carcinomas. Clinically, there was no evidence of nevus sebaceus, xeroderma pigmentosum, basal cell nevus syndrome, or immunodeficiency. Clinical workup including chest radiography, abdominal ultrasound, bone scan, and brain computerized axial tomography scan did not demonstrate primary or secondary tumors. The results of serologic and hematologic tests were also within normal limits. This is an unusual case report of multiple pigmented basal cell carcinomas in an Asian woman without any predisposing risk factors.
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PMID:Multiple pigmented basal cell carcinomas. 955 92

In advanced skin carcinomas of the head and neck region, the tumor may be unresectable or curative resection or radiation may either fail or produce poor functional and cosmetic results. The goal of this study was to test the ability of preoperative chemotherapy to decrease the extent of needed resection and tumor response. Five patients, three with squamous cell carcinoma and two with basal cell carcinoma, were treated before surgery with three cycles of cisplatin 20 mg/m2 daily for 4 days and bleomycin 20 mg/day for 4 days by continuous infusion every 3 weeks. All patients had advanced cancer in the head and neck region, one had unresectable tumor, two had xeroderma pigmentosum, and one was a 13-year-old child. The history of prior treatments was as follows: radiation therapy (n = 3), systemic chemotherapy (n = 1), surgery (n = 1), and no treatment (n = 1). One patient had complete clinical but not pathologic response, three had partial response, and one had progressive disease. The extent of resection after chemotherapy was dramatically reduced in the patient with a complete response and minimally changed in the patients with partials responses and progressive disease. All patients who underwent surgery became tumor free. Preventable toxicity was symptomatic hypomagnesemia in one patient, reversible elevation of creatinine in one patient, and mild nausea and vomiting in three patients. With this report, the total number of patients with nonmelanoma skin cancer who were treated with cisplatin is 68, and their overall response is 80%. Only 16 reported patients were treated with preoperative chemotherapy, and study of this treatment approach to advanced skin cancer should be pursued.
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PMID:Preoperative treatment of advanced skin carcinoma with cisplatin and bleomycin. 1002 76

Basal cell carcinoma is the most frequent of all cancers. Its incidence has risen those last decades because of the increase in sun exposure habits. People with light skin complexion are particularly at risk. Ionizing radiations, arsenicism, various genodermatoses (Gorlin syndrome, xeroderma pigmentosum, nevus sebaceous) are other pre-disposing factors. Basal cell carcinoma usually present as small lesion with a pearly border and telangiectasias. Other clinical types must also be recognized such as the nodular, the infiltrative, the superficial and the pigmented forms. They are usually located on the head and trunk. The prognosis of basal cell carcinoma is usually good since they can be cured by surgical excision and because they usually do not metastasize. However, large, multiple or recurrent basal cell carcinomas can be difficult to treat. In these cases, cryosurgery, radiotherapy or intralesional interferon-alfa may be needed.
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PMID:[Basal cell carcinoma]. 1033 93

Cancer initiation is classically associated with the induction of mutations on specific oncogenes or tumor suppressor genes, due to the presence of unrepaired DNA lesions produced by endogenous or exogenous genotoxic agents. Among several DNA repair pathways, the nucleotide excision repair (NER) is the most important and versatile one in removing the bulky adducts induced by physical and chemical carcinogens. Xeroderma pigmentosum (XP), characterized by a deficiency in NER and an over 1000-fold increased risk of skin cancer, represents a paradigm to understand the role of unrepaired lesion in the development of cancer. We reviewed here several NER assays used in epidemiological studies investigating the association between DNA repair efficiency and cancer risk. Reduced DNA repair could contribute to the development of cutaneous basal cell carcinoma (BCC), although discordant results have been reported. More consistent findings were observed between cellular sensitivity towards genotoxic agents and smoking-related cancers.
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PMID:Variability in nucleotide excision repair and cancer risk: a review. 1076 26

Germline mutations of the human patched gene, PTCH, are responsible for the nevoid basal cell carcinoma (NBCC) syndrome or Gorlin's syndrome, characterized by multiple skin cancers, internal cancers and severe developmental abnormalities. The patched gene codes for a developmental regulator protein implicated in the sonic hedgehog (SHH) signalling pathway which plays an important role in oncogenic transformation. Patched exhibits tumor suppression function and has been shown to be mutated in skin cancers isolated from DNA repair-proficient patients or from xeroderma pigmentosum (XP), a DNA repair-deficient syndrome. We have reviewed and analyzed in detail the different mutation spectra found on the PTCH gene in these various models. The type and distribution of mutations are quite different between germline, sporadic and XP cancers. Among the germline alterations, there is a preponderance (70%) of rearrangements compared to other tumour types analysed where less than 30% of rearrangements is observed. Typical UV-induced mutations of the patched gene are found prominently in XP basal cell carcinomas (BCCs) and in particular, a significantly higher level (63%) of the UV signature tandem mutations is found compared to sporadic BCC (11%). The location of mutations along the PTCH protein delineates several important functional domains implicated in the biology of this transmembrane receptor.
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PMID:UV-specific mutations of the human patched gene in basal cell carcinomas from normal individuals and xeroderma pigmentosum patients. 1083 43

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

Xeroderma pigmentosum has not been reported in association with any specific diseases except for skin malignancy. We observed a case of its coexistence with sarcoidosis and adenocarcinoma of the digestive organs, which has been reported only once in the past. A 54-year-old Japanese female with a variant type of xeroderma pigmentosum developed successively multiple lesions of basal cell carcinoma and squamous cell carcinoma on her face. Intensive metastasis studies led to the incidental detection of non-caseating epithelioid cell granulomas in one of the palpable right supraclavicular lymph nodes. Similar granulomas were also revealed in the excised tissue specimen of squamous cell carcinomas of her left cheek. She was also found to have bilateral hilar lymphadenopathy and chronic uveitis. Three years later, she died of colon adenocarcinoma and its liver metastasis.
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PMID:Coexistence of xeroderma pigmentosum with sarcoidosis and adenocarcinoma of the digestive organs. 1120 Aug 39

We report 6 cases of black Senegalese boys with xeroderma pigmentosum. They were between 2 and 16 year-old and presented features of hypersensitivity to UV (keratosis, lentigines, poikilodermia and photophobia). Our cases were remarkable by the early occurrence of squamous cell and basal cell carcinoma located in photoexposed sites causing the death of 5 of them. Xeroderma pigmentosum must be considered as the first preneoplastic genodermatosis.
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PMID:[Xeroderma pigmentosum: report of 6 cases in Dakar]. 1125 94


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