Relationship Between p53 Codon 72 Polymorphism and Susceptibility to Sunburn and Skin Cancer

• Published in: Journal of investigative dermatology Vol. 119; no. 1; pp. 84 - 90
• Main Authors: McGregor, Jane M., Harwood, Catherine A., Brooks, Louise, Kelly, Deirdre A., O’nions, Jenny, Young, Antony R., Surentheran, Thiru, Breuer, Judith, Millard, Thomas P., Lewis, Cathryn M., Leigh, Irene M., Storey, Alan, Crook, Timothy, Fisher, Sheila A.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-07-2002; Nature Publishing; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Dermatology; DNA, Viral - analysis; Genetic Predisposition to Disease - epidemiology; Genotype; human papillomavirus; Humans; Immunocompetence; Immunosuppression; Kidney Transplantation; Loss of Heterozygosity; Medical sciences; Middle Aged; nonmelanoma skin cancer; Papillomaviridae - genetics; Papillomaviridae - isolation & purification; Papillomavirus Infections - epidemiology; Polymorphism, Single Nucleotide; renal transplantation; Risk Factors; Skin Neoplasms - epidemiology; Skin Neoplasms - genetics; Sunburn - epidemiology; Sunburn - genetics; Tumor Suppressor Protein p53 - genetics; Tumor Virus Infections - epidemiology; Tumors of the skin and soft tissue. Premalignant lesions; ultraviolet radiation; ultraviolet radiation; nonmelanoma skin cancer; immunosuppression; renal transplantation; human papillomavirus; Human; Skin disease; Typing; Malignant tumor; Trauma; Carcinogenesis; Burn; Polymerase chain reaction; TP53 Gene; Predisposition; Cytogenetics; Skin; Molecular biology; Erythema; Solar radiation; Tumor suppressor gene; Polymorphism
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.1523-1747.2002.01655.x

Upregulation of p53 protein induces either growth arrest or apoptosis in response to cellular injury This is signaled from a highly conserved p53 domain between codons 64 and 92, where a functional polymorphism results in either a proline (p53-72P) or an arginine (p53-72R) at codon 72. Preliminary studies suggest that p53-72R may be a risk factor for cervical cancer and, consistent with this, preferential mutation and retention of the p53-72R allele has also been demonstrated in other cancers of squamous cell origin. Here we examine the relationship between allelic forms of p53 and nonmelanoma skin cancer, by determining the correlation with susceptibility to sunburn, which is a known risk factor, and then by p53 sequence analysis of a large series of tumors. We found a significant positive association between p53-72R and susceptibility to sunburn, as assessed by skin phototype and minimal erythemal dose following solar-simulated radiation (p = 0.0001 for trend). We also found a significant association between p53-72R homozygosity and nonmelanoma skin cancer in renal transplant recipients (basal cell carcinoma, p < 0.01; squamous cell carcinoma, p < 0.05) but not in immunocompetent patients compared with skin type matched controls. p53 sequence data revealed mutations in 30 of 70 (42.9%) nonmelanoma skin cancers, 28 (93%) of which were in the p53-72R allele. Loss of heterozygosity occurred more frequently in p53-72RP than in p53-72RR tumors (p = 0.0001) with preferential loss of p53-72P in heterozygotes (p = 0.016), irrespective of the mutant status of the concomitant allele. Together these data infer functional differences between polymorphic forms of p53 that are likely to be relevant to skin carcinogenesis.