Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 65-year-old Japanese man with a xeroderma pigmentosum (XP) variant, XP127TO, is described. The XP127TO skin fibroblasts exhibited the typical XP variant characteristics of a 1.5-fold higher sensitivity than normal cells to the lethal effect of 254 nm ultraviolet (UV) light and the normal level of unscheduled DNA synthesis induced by 254 nm UV. Caffeine dose-dependently increased the cytotoxic effect of 254 nm UV on XP127TO cells. Clinically, the patient developed not only 3 cutaneous squamous cell carcinomas on sun-exposed areas but also an adenocarcinoma of the upper lobe of the right lung. A review of the 14 documented Japanese XP patients with nonskin malignancies indicates that the incidence of nonskin malignancy in XP patients is much lower than that of skin cancer in XP but higher than that in the general population.
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PMID:Xeroderma pigmentosum variant associated with multiple skin cancers and a lung cancer. 139 8

Skin fibroblasts from ataxia telangiectasia and xeroderma pigmentosum (XP) donors and from the XP sib (possible heterozygote), all genetically predisposed to a high risk of cancer, show an increased susceptibility to light-induced chromatid breaks after culture in vitro. Light-induced chromatid breaks were shown previously to result from generation of hydrogen peroxide (H2O2) during light exposure. The level of susceptibility attained is significantly higher than that observed in 13 lines of fibroblasts from normal skin of donors ranging in age from 3 days to 92 years or from fetal skin tested at various population doubling levels. Two lines of normal skin fibroblasts transformed by chemical carcinogens to neoplastic cells also show a significant increase in susceptibility as compared with their untransformed controls. These data indicate for human cells, as reported earlier for mouse cells, an association between enhanced susceptibility to light-induced chromatid damage and neoplastic potential; this association is further supported by the high susceptibility of cells derived from a human adenocarcinoma. Two observations are consistent with the concept that the increased susceptibility does not result from greater initial damage to the DNA of the neoplastic cells. First, activities of the ubiquitous H2O2 scavenging enzyme, glutathione peroxidase, are similar in the paired normal and neoplastic cell populations. Second, cells of the paired lines are equally sensitive to DNA breakage by exogenous H2O2. The enhanced susceptibility associated with neoplastic potential may result from an impaired capacity to repair DNA rather than a greater initial sensitivity of the neoplastic cells to the damaging agent.
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PMID:Light-induced chromatid damage in human skin fibroblasts in culture in relation to their neoplastic potential. 731 76

Precancerous skin lesions are categorized into three groups; (1) carcinoma in situ, (2) hereditary precancerous lesions, and (3) non-hereditary precancerous lesions. Carcinoma in situ includes Bowen's disease, actinic keratosis and leukoplakia as squamous cell carcinoma in situ, Paget's disease as adenocarcinoma in situ, and melanoma in situ. Hereditary precancerous lesions include xeroderma pigmentosum, epidermodysplasia verruciformis and porokeratosis. The mechanisms of carcinogenesis in these diseases are investigated intensively. Chronic radiodermatitis and other scars are treated as non-hereditary precancerous lesions.
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PMID:[Reevaluation of precancerous lesions of the skin]. 860 16

Fifty-eight skin biopsies and three primary internal tumors from patients affected by the rare hereditary disease xeroderma pigmentosum (XP) were studied by an improved PCR-single strand conformation polymorphism analysis to detect the mutations of the tumor suppressor gene p53. The results from cutaneous XP tumors, including 27 squamous cell carcinomas and 6 basal cell carcinomas, show a very high level (86%) of p53 mutations. The analysis of mutations found in XP skin cancers according to the complementation group of the patients shows that tandem CC-->TT transitions are a characteristic of XP-C patients with a frequency much higher in their skin tumors (85%) compared with tumors in XP patients who do not belong to group C (33%). In all XP-C biopsies, mutations were due to replication of unrepaired DNA lesions on the nontranscribed strand of the p53 gene, substantiating the preferential repair in vivo of the transcribed strand of this gene in human tissues. For the first time, we were able to analyze three primary internal tumors (a neuroendocrine tumor of the thyroid, a gastric adenocarcinoma, and a glioma of the brain) of young XP children. All of them contained one mutation on the p53 gene, which were different from the ones found in the XP skin tumors and could have resulted from unrepaired lesions caused by oxidative damage.
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PMID:p53 mutations in skin and internal tumors of xeroderma pigmentosum patients belonging to the complementation group C. 976 70

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

Xeroderma pigmentosum (XP) is an inherited disease with defective DNA repair. Patients develop skin cancer because of unrepaired DNA damage produced by the ultraviolet radiation (UV) in sunlight. Many XP children also develop XP neurological disease (ND), consisting of sensorineural hearing loss (SNHL) and a primary neuronal degeneration of the central and peripheral nervous systems. Since the harmful UV in sunlight cannot reach the nervous system, the cause of the death of XP neurons has been hypothesized to result from the inability to repair their DNA that has been damaged by endogenous metabolites. Progressive XP ND originating in an adult has been identified in only a single case. Although clinically asymptomatic at the age of 47 years, the patient had audiometric evidence of a developing mild SNHL together with elicited signs and electrophysiologic evidence of a peripheral neuropathy. She died of metastatic endocervical adenocarcinoma at 49 years of age. We describe here the neuropathological findings in this patient, including examination of the inner ear. Despite clinical evidence of SNHL, there were no anatomic abnormalities of the inner ear. However, the dorsal root ganglia (DRG) showed ongoing neuronal loss. Our findings indicate that XP ND originating in this adult is, like XP ND in children, a primary neuronal degeneration that manifests first in the peripheral nervous system.
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PMID:Adult-onset xeroderma pigmentosum neurological disease--observations in an autopsy case. 1184 40

DNA repair plays a critical role in protecting the genome from insults of cancer-causing agents, such as those found in tobacco smoke. Therefore, reduced DNA repair capacity can increase the susceptibility to smoking-related cancers. Recently, several polymorphisms have been identified in the xeroderma pigmentosum group G (XPG) gene, and it is possible that these polymorphisms may affect the DNA repair capacity, thereby modulating cancer susceptibility. We investigated the relationship between the His1104Asp polymorphism in the XPG gene and the risk of lung cancer. The study population consisted of 310 lung cancer patients and 311 healthy controls who were frequency (1:1) matched based on age and sex. The Asp/Asp genotype was more frequent in the controls (28.9%) than in the cases (18.7%) and associated with a significantly decreased risk of lung cancer [adjusted odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37-0.80] when the combined His/His and His/Asp genotype was used as the reference. The protective effect of the Asp/Asp genotype against lung cancer was statistically significant in the older subjects (adjusted OR = 0.51, 95% CI = 0.37-0.80), males (adjusted OR = 0.54, 95% CI = 0.35-0.83), and lighter smokers (adjusted OR = 0.48, 95% CI = 0.25-0.94) in a stratification analysis. When the lung cancers were analyzed by histologic type, the Asp/Asp genotype was associated with a significantly decreased risk of squamous cell carcinoma (adjusted OR = 0.55, 95% CI = 0.34-0.88) and small cell lung cancer (adjusted OR = 0.44, 95% CI = 0.20-0.97), but non-significant decreased risk of adenocarcinoma (adjusted OR = 0.64, 95% CI = 0.36-1.12). These results suggest that the XPG codon 1104 polymorphism contributes to genetic susceptibility to lung cancer.
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PMID:Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer. 1286 23

DNA damage is important in the pathogenesis of esophageal adenocarcinoma (EA). Polymorphic variants in DNA repair genes may be modifiers of the risk of EA through their role in altering human host response to gastroesophageal acid reflux, a well-described risk factor for EA. We studied the role of genetic polymorphisms of two key DNA repair genes, xeroderma pigmentosum group D (XPD) (Asp312Asn and Lys751Gln) in the nucleotide excision repair (NER) pathway and X-ray repair cross-complementing gene 1 (XRCC1) (Arg399Gln) in the base excision repair (BER) pathway, in the development of EA in 183 cases and 336 frequency-matched controls for age, gender and race. Genomic DNA was extracted from blood samples. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from logistic regression models, adjusted for body mass index at 18 years of age, smoking and alcohol exposure. The variant genotypes of XPD Lys751Gln polymorphism were associated with a higher risk of EA; the adjusted OR comparing Gln/Gln + Lys/Gln with Lys/Lys was 1.49 (95% CI: 1.02-2.14). Although no significant relationships were found for the XRCC1 Arg399Gln polymorphism alone, this polymorphism did modify the relationship between XPD Lys751Gln and EA risk; when both polymorphisms were evaluated together, adding the number of variant alleles of the two polymorphisms resulted in a significant trend (trend test, P = 0.008); compared with individuals with no variant alleles (n = 88), the adjusted ORs of developing EA are 1.49 (95% CI: 0.88-2.59), 1.69 (95% CI: 0.98-2.96) and 2.58 (95% CI: 1.31-5.06) for one (n = 195), two (n = 166) and three or four variant alleles (n = 70), respectively. No relationships were found for the XPD Asp312Asn polymorphism. We conclude that combined NER and BER pathways are important to the development of EA.
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PMID:XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk. 1726 68

Reflux of gastric contents can lead to development of reflux esophagitis and Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal adenocarcinoma. Damage to DNA may lead to carcinogenesis but is repaired through activation of pathways involving polymorphic enzymes, including human 8-oxoguanine glycosylase 1 (hOGG1), X-ray repair cross-complementing 1 (XRCC1), and xeroderma pigmentosum group D (XPD). Of the single nucleotide polymorphisms identified in these genes, hOGG1 Ser 326 Cys, XRCC1 Arg 399 Gln, and XPD Lys 751 Gln are particularly common in Caucasians and have been associated with lower DNA repair capacity. Small studies have reported associations with XPD Lys 751 Gln and esophageal adenocarcinoma. XRCC1 Arg 399 Gln has been linked to Barrett's esophagus and reflux esophagitis. In a population-based case-control study, we examined associations of the hOGG1 Ser 326 Cys, XRCC1 Arg 399 Gln, and XPD Lys 751 Gln polymorphisms with risk of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis. Genomic DNA was extracted from blood samples collected from cases of esophageal adenocarcinoma (n = 210), Barrett's esophagus (n = 212), reflux esophagitis (n = 230), and normal population controls frequency matched for age and sex (n = 248). Polymorphisms were genotyped using TaqMan allelic discrimination assays. Odds ratios and 95% confidence intervals were obtained from logistic regression models adjusted for potential confounding factors. There were no statistically significant associations between these polymorphisms and risk of esophageal adenocarcinoma, Barrett's esophagus, or reflux esophagitis.
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PMID:No association between hOGG1, XRCC1, and XPD polymorphisms and risk of reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma: results from the factors influencing the Barrett's adenocarcinoma relationship case-control study. 1834 97

The published data on the association between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism and esophageal cancer (EC) remained controversial. The present meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A comprehensive literature search was conducted to identify all case-control studies of Lys751Gln polymorphism and risk for two main types of EC: esophageal adenocarcinoma (EADC) and esophageal squamous cell carcinoma (ESCC). A total of 12 studies were identified to the meta-analysis, including 2,575 cases (1,294 ESCC and 1,281 EADC) and 4,951 controls (1,891 ESCC and 3,060 EADC). Random-effects or fix-effects model was used according to between-study heterogeneity. The odds ratio (OR) for the variant homozygous genotype Gln/Gln of the Lys751Gln polymorphism, compared with the wild type homozygote Lys/Lys, was 1.26, with 95% confidence interval (95% CI) 1.02-1.56, for EADC risk without between-study heterogeneity. When stratified by ethnicity, statistically significantly elevated risk was found among Chinese (Gln/Gln vs. Lys/Lys: OR 2.45, 95% CI = 1.10-5.44). However, no significant associations were found between XPD Lys751Gln polymorphism and EC risk when all studies pooled into the meta-analysis (Lys/Gln vs. Lys/Lys: OR 1.07, 95% CI = 0.88-1.28; Gln/Gln vs.us Lys/Lys: OR 1.25, 95% CI = 0.92-1.71; dominant model: OR 1.09, 95% CI = 0.90-1.33). In conclusion, this meta-analysis suggests that the Lys751Gln genetic polymorphism may be a potential biomarker of EC susceptibility in Chinese populations. And a study with the larger sample size is needed to further evaluate gene-environment interaction on XPD Lys751Gln polymorphism and EC risk.
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PMID:XPD Lys751Gln polymorphism and esophageal cancer susceptibility: a meta-analysis of case-control studies. 2166 12


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