Early-onset of sporadic basal-cell carcinoma: Germline mutations in the TP53, PTCH, and XPD genes

Edu B. Suárez-Martínez, Abigail Ruiz, Jocelyn Matias, Luisa Morales, Anayris Cruz, Deborah Vázquez, Jaime Villa, Jaime L. Matta


Background: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer in the Western world. The objective of this study was to examine together germline mutations in the TP53, PTCH, and XPD genes as risk factors for developing BCC at a young age. We hypothesized that mutations in these genes significantly increase the risk of early-onset BCC ( < 35 years). Methods: The PCR, DNA sequencing and Restriction Fragment Length Polymorphisms methods were utilized to study eight Puerto Rican patients with a confirmed diagnosis of BCC before age 35. Results: A novel germline mutation (T:A transversion) was identified at the exon 4, codon 50 of the TP53 gene of one BCC patient. No other mutations were found at the TP53 or PTCH genes. The presence of the XPD mutant allele is associated with a seven-fold increase in risk (OR=7.0, p=0.03) for developing BCC prior to age 35. In addition, the DNA Repair Capacity (DRC) of these BCC patients showed a 47% reduction that was significant in relation to age-matched controls (p=0.021). However, the XPD mutant allele was not associated with the decrease in DRC observed in BCC participants. Conclusions: The evaluated population presented BCC before age 35, a phenomenon that is so rare, as to make very difficult the study of this subpopulation with a larger sample size. The results of this study, suggest that the XPD Lys751Gln polymorphism may have a significant role in the development of early-onset BCC in the Puerto Rican population.

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