Xeroderma pigmentosum, skin cancer

Currently, 13-cis-retinoic acid is the most studied chemopreventive agent that decreases the incidence of second primary tumors in patients with head-and-neck cancer, reverses premalignant lesions, and reduces appearance of nonmelanoma skin cancer in patients with xeroderma pigmentosum. Unfortunately, this vitamin A derivative has a significant clinical toxicity, which limits its utility in a practice setting. 

Defects have been found in these mechanisms that cause various human diseases. For example, patients with the genetic disease xeroderma pigmentosum are especially sensitive to ultraviolet light and develop skin cancer. Skin fibroblasts cultured from these patients have been shown to be defective in DNA repair. 

Xeroderma pigmentosum is an autosomal recessive disorder, characterized by extreme sensitivity to sunlight, skin freckling and ulcerations, and skin cancer. The most common defidency occurs in the excinudease enzyme. 

Yarosh, D., et al.. Effect of topically apphed T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum a randomised smdy. Lancet, 357, 926-29, 2001. 

Patients with xeroderma pigmentosum are prone to develop skin cancer later in life. 

The answer is B. The patient has many of the features characteristic of xeroderma pigmentosum. The lesion, hyperpigmentation (freckles), and erythema are located over sun-exposed areas. His corneas have also suffered damage from exposure to ultraviolet irradiation from the sun. His photosensitivity is also manifested in easy sun-burning and aversion to sun exposure. This condition often leads to skin cancer. 

It is also clear that apart from exposure to carcinogens, other factors such as the genetic predisposition of the organism exposed may also be important. Thus, patients with the genetic disease xeroderma pigmentosum are more susceptible to skin cancer. It has already been mentioned that the incidence of bladder cancer is significantly higher in those individuals who have the slow acetylator phenotype. 

In the rare genetic disease xeroderma pigmentosum, the cells cannot repair the damaged DNA, resulting in extensive accumulation of mutations and, consequently, skin cancers (Figure 29.28). The most common form of this disease is caused by the absence of the UV-specific excinuclease. 

Excision repair in mammalian cells is considered to occur by a similar mechanism. Inherited defects in this repair pathway can lead to the disease xeroderma pigmentosum, in which the skin is very sensitive to sunlight and results in a high incidence of skin cancer. 

Patients with xeroderma pigmentosum develop skin cancer when they are exposed to sunlight because they have a deficiency in... 

Human disease may result from inability to carry out certain stages of DNA repair. The best studied disease, xeroderma pigmentosum, is a result of mutations in genes that encode the UV excision system. Cells cultured from tissue obtained from affected individuals are killed by much smaller doses of UV light than are normal cells. Furthermore, the removal of thymine dimers in DNA from these cells is very inefficient. People with this disease develop skin lesions when exposed to sunlight and commonly develop one of several kinds of skin cancer. 

A 48-year-old man has had a lengthy history of skin cancer. In the past 6 years he has had over 30 neoplasms removed from sun-exposed areas and has been diagnosed with xeroderma pigmentosum. Which of the following best describes the enzymatic defect in patients with xeroderma pigmentosum ... 

By contrast, deficiencies in GG-NER (see Section 11.3) lead to the inherited disorder xeroderma pigmentosum (XP), which can be viewed as the prototypical DNA repair disorder [7-9]. XP patients are unable to repair UV lesions, and as a consequence suffer from an extreme sensitivity to UV light and an over 1000-fold increased incidence of skin cancer. Severely affected XP patients additionally suffer from neurological abnormalities. The phenotypes of two additional symptoms associated with NER genes, Cockayne syndrome (CS) and trichothiodystro-phy (TTD), are more complex as they are due to defects in transcription as well as defects in DNA repair [10]. 

Exposure to UV radiation from sunlight is the major cause of human skin cancer. Skin tumors from patients with Xeroderma pigmentosum, a DNA-repair deficiency associated with increased sensitivity to UV, show a particularly high frequency of these CC to TT transitions (Dumaz et al., 1993). Mutations at dipyrimidines have been observed in the normal skin of sun-exposed skin cancer patients (Jonason et al., 1996 Nakazawa et al., 1994 Ren et al., 1996a). The localization of mutations in skin shows striking differences with other types of cancers, with hotspots at codons 177-179 and... 

The rare skin condition. Xeroderma pigmentosum (XP), is characterised by extreme sensitivity to sunlight and a predisposition to skin cancer. Cells taken from persons suffering from this condition are more sensitive to UV-irradiation than normal cells and are deficient in excision repair of UV-induced damage. These same cells are also sensitive to other DNA damaging agents such as hydrocarbon epoxides, 4-nitroquinoline-l-oxide and... 

Nucleotide Excision Repair Was Elucidated Through Study of Xeroderma Pigmentosum, a Hereditary Predisposition to Skin Cancers... 

Inherited defects in the nucleotide excision-repair pathway, as in individuals with xeroderma pigmentosum, predispose them to skin cancer. Inherited colon cancer frequently is associated with mutant forms of proteins essential for the mismatch repair pathway. 

The human genetic disease, xeroderma pigmentosum (XP), is a defect in DNA repair of thymine dimers. This condition results in extreme sensitivity to sunlight with a predisposition to skin cancer. Genetic... 

There are several genetically determined diseases such as xeroderma pigmentosum (XP), Fanconi s anemia. Bloom s syndrome, ataxiatelangiectasia and porokeratosis Mibelli in which individuals have an increased if not an invariable incidence of cancer (291. These diseases are associated with DNA repair defects, thought to be the cause of the cancer sensitivity (291. In the case of a person with XP, the oversensitivity of the skin to ultraviolet light is inherited and the condition leads to skin cancer. 

A human excinuclease cleaves at positions -22 and +6 relative to a thymine dimer. A significant difference between this and the UvrABC enzyme is the involvement of two different endonucleases--one for cutting on the 5 side and one on the 3 side. The disease, xeroderma pigmentosum (XP), is actually a family of diseases, in which one or more enzymes of the excision pathway are deficient. The biological consequences of XP include extreme sensitivity to sunlight and a high incidence of skin cancers. In affected humans, there is at present no known way to treat the condition. 

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