Xeroderma Pigmentosum: A Genetic Condition Skin Cancer Correlated—A Systematic Review

Abstract

Background. Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of UV radiation-induced damage repair that is characterized by photosensitivity and a propensity for developing, among many others, skin cancers at an early age. This systematic review focused on the correlation between the clinical, pathological, and genetic aspects of XP and skin cancer. Methods. A systematic review was conducted through a literature search of online databases PubMed, Cochrane Library, SciELO, and Google Scholar. Search terms were “Xeroderma pigmentosum”, “XP”, “XPC”, “Nucleotide excision repair”, “NER”, “POLH”, “Dry pigmented skin”, and “UV sensitive syndrome” meshed with the terms “Skin cancer”, “Melanoma”, and “NMSC”. Results. After 504 abstracts screening, 13 full-text articles were assessed for eligibility, and 3 of them were excluded. Ten articles were selected for qualitative assessment. Conclusions. Patients with XP usually suffer shorter lives due to skin cancer and neurodegenerative disease. Deletion/alteration of a distinct gene allele can produce different types of cancer. The XPC and XP-E variants are more likely to have skin cancer than patients in other complement groups, and the most common cause of death for these patients is skin cancer (metastatic melanoma or invasive SCC). Still, aggressive preventative measures to minimize UV radiation exposure can retard the course of the disease and improve the quality of life.

Association of Single-Nucleotide Polymorphisms of Gene XPC with Susceptibility to Basal Cell Carcinoma in Brazilian Population

“…They found that the G allele of polymorphism rs1800975 is associated with an increased risk of BCC and SCC and the seven haplotypes were in the Hardy-Weinberg equilibrium. This was the first study to relate polymorphisms in the XPA gene with the predisposition to the development of non-melanoma skin cancer [15]. Differently from Miller et al [15], Ding et al performed a meta-analysis to analyze the association of rs1800975 polymorphism with cancer risk.…”

“…This was the first study to relate polymorphisms in the XPA gene with the predisposition to the development of non-melanoma skin cancer [15]. Differently from Miller et al [15], Ding et al performed a meta-analysis to analyze the association of rs1800975 polymorphism with cancer risk. They verified that of the 36 control cases analyzed, in general there was no significant association between the polymorphism and the susceptibility to develop cancer.…”

“…XPC recognizes and binds to damaged DNA, interacts with hHR23 to protect itself from proteolytic degradation, interacts with CENTN2 to increase its binding affinity for DNA. It recruits the TFIIH, which acts as a helicase and together with the RPA constitutes the pre-incision complex, opening the double helix [12][13][14][15].…”

Polymerase iota plays a key role during translesion synthesis of UV‐induced lesions in the absence of polymerase eta

“…Mutations in specific NER genes cause the genetic syndrome xeroderma pigmentosum (XP), characterized by hypersensitivity to UV radiation, increased incidence of tumors in areas exposed to sunlight, and, in 20%-30% of the patients with XP, progressive neurodegeneration. [7][8][9][10][11][12] Photoproducts may persist in cells undergoing DNA replication even in NER-proficient cells. Therefore, CPDs may block replicative DNA polymerases, generating cellular stress and a fragile structure in the replication fork, 4,5,13 while 6-4PPs are usually repaired in a few hours.…”

“…Different mechanisms emerged during evolution to resolve these lesions, and the primary repair pathway in mammalian cells is nucleotide excision repair (NER). Mutations in specific NER genes cause the genetic syndrome xeroderma pigmentosum (XP), characterized by hypersensitivity to UV radiation, increased incidence of tumors in areas exposed to sunlight, and, in 20%–30% of the patients with XP, progressive neurodegeneration 7–12 …”