p53 codon 72 polymorphism and human papillomavirus associated skin cancer

Abstract

Background/Aims-Non-melanoma skin cancers frequently harbour multiple human papillomavirus (HPV) types. A recent report suggests that a polymorphism of the p53 tumour suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in HPV associated malignancies. This study aimed to determine the following: (1) the relation between HPV infection and the development of cutaneous squamous cell carcinoma (SCC), and (2) whether there is a correlation between p53 codon 72 polymorphism and the development of SCC. Methods-Blood samples were taken from 55 patients with skin cancer (both renal transplant recipients and immunocompetent patients with skin cancer) and 115 ethnically matched volunteers. A polymerase chain reaction based assay was used to determine p53 codon 72 genotypes. In addition, 49 benign and malignant lesions from 34 of the patients with skin cancer and 20 normal human skin samples from 20 of the control volunteers were examined for HPV. Results-The proportions of p53 codon 72 genotypes found were 78% arginine homozygous, 2% proline homozygous, and 20% heterozygous among patients with skin cancer and 79% arginine homozygous, 3.5% proline homozygous, and 17.5% heterozygous among the control population. Statistical analysis showed no significant diVerences in the distribution of the two p53 isoforms between the patients with skin cancer and the control population. The predominant viral types detected in both the patients and the control group were EV associated HPVs, although the incidence was lower in normal skin samples than in malignant lesions or viral warts. Conclusions-These results suggest that in a Celtic population there is no correlation between the presence of HPV, the p53 codon 72 arginine polymorphism, and the development of skin cancer. (J Clin Pathol 2001;54:539-542) Keywords: p53 codon 72 polymorphism; human papillomavirus; skin cancer Non-melanoma skin cancers (NMSCs) are the most frequent cancers in white populations. NMSCs often harbour multiple human papillomaviruses (HPVs), although a causal role for the virus in cutaneous tumorigenesis is yet to be confirmed. A recent report 1 suggests that a common polymorphism at codon 72 of the p53 tumour suppressor gene 2 might be a risk factor in the development of HPV associated cancers. The replacement of a proline residue with an arginine residue at position 72 of the p53 gene product marginally increased the susceptibility of the protein to degradation by the E6 oncoprotein of high risk HPV types 16 (HPV-16) and 18. The presence of an arginine residue was also found to increase greatly the susceptibility of p53 to degradation by the E6 protein of low risk HPV type 11.Subsequent reports 3 4 demonstrated that individuals who were homozygous for the arginine variant of the protein were at no greater risk of developing cervical cancer. However, one report suggests that in Swedish and Italian women with HPV-16 positive cervical disease, the inci...

The Role of Human Papillomaviruses in the Development of Non-Melanoma Skin Cancers

“…18,25,31 Although no particular HPV type recognized as significantly associated with NMSC in immunocompetent patients to date, beta HPV types has been detected predominantly in the malignant and premalignant lesions of these patients. 3,13,18,25,26 Consistent with the literature, we detected HPV Type 5 in one AK specimen, but the HPV detected in BCC specimen could not be typed.…”

“…3,20,21,23,24 Despite no HPV type has emerged specifically to be associated with skin cancer, beta HPV types have been detected predominantly in the lesions. 3,13,18,[25][26][27] The establishment of the relationship between the NMSC and HPV provide a basis for not only the preventive measures like vaccination but also improvement of antiviral/antitumor treatment. Characterization of HPV types that are significantly related with skin cancer is important especially for development of vaccine against these tumors.…”

Risk of Cutaneous Squamous Cell Carcinoma Development in Renal Transplant Recipients Is Independent of <b><i>TMC/EVER</i></b> Alterations

“…Examination of a further SNP (rs1042522 in the TP53 gene), suggested to be involved in cSCC development [20], showed no correlation with cSCC risk in RTRs, which is consistent with a single report [36] and a recently published meta-analysis [37]. …”

p53 codon 72 polymorphism in coronary artery disease: No evidence for association with increased risk or micronucleus frequency

“…By contrast, the inheritance of the arginine allele appears to be involved in the development of human-papillomavirusassociated cancer [Storey et al, 1998;Kawaguchi et al, 2000]. Finally, some reports suggest that the codon 72 alleles do not have a significant impact on human cancer risk [Sun et al, 1999;Bastiaens et al, 2001;O'Connor et al, 2001;Tandle et al, 2001].…”