Germline mutations in CDKN2A and/or red hair color variants in MC1R genes are associated with an increased susceptibility to develop cutaneous melanoma or non melanoma skin cancer.
The MC1R gene is highly polymorphic in Caucasian populations with a number of MC1R variant alleles associated with red hair, fair skin, freckling, poor tanning, and increased risk of melanoma and nonmelanoma skin cancer.
Finally, we examine recent work showing that loss-of-function MC1-R variants may increase the risk of developing melanoma and nonmelanoma skin cancer beyond their effects on pigmentation phenotype.
To analyze the association between melanocortin 1 receptor gene variants and skin type or hair color we also made use of 453 patients with nonmelanoma skin cancer.
We investigated whether subjects with MC1R variant alleles were at increased risk of developing nonmelanoma skin cancer and, if so, whether this increased risk was mediated by fair skin and red hair.
The mutation pattern detected in the Tg skin lesions closely resembles that detected in human NMSC, with the highest mutation rate in p53 and Notch genes.
As MMR enzyme hMSH2 displays a p53 target gene, is induced by UVB radiation and is involved in NER pathways, studies have now been initiated to elucidate the physiological and pathophysiological role of MMR in malignant melanoma and nonmelanoma skin cancer development.
This report shows that much of the 682-gene signature of this murine skin carcinoma transcriptome is also present in breast and lung cancer mouse models in which p53 is inhibited.
Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer.
In total, there was no significant difference in the p53 codon 72 genotypes between histological types of NMSC, gender, race, tumor location and age group.
In 902 cases of basal cell carcinoma (BCC), 676 cases of squamous cell carcinoma (SCC) and 812 controls, no association was found between the TP53 polymorphism and risk of non-melanoma skin cancer [odds ratio (OR)(BCC) 0.98, 95% confidence interval (CI) 0.80-1.20; OR(SCC) 0.93, 95% CI 0.75-1.16].
We observed abnormal p53 accumulation in over half of the samples analysed (55.5%), suggesting it to be a major part of the carcinogenic process of NMSC; however; there was no association between p53 positivity and the presence of mtDNA mutations (P = 0.47).
Moreover, we propose up-regulated wild-type p53 together with p76(MDM2) as major players in the control of DNA damage/repair and prevention of photodamage and nonmelanoma skin cancer in vitiligo.
The mechanism by which the E6 protein of cutaneous HPV types interacts with cellular proteins to induce either benign or malignant cutaneous lesions, has not been elucidated, although extensive ultraviolet exposure and mutated p53 (hot-spot mutations) are known to be associated with non-melanoma skin cancer.
As MMR enzyme hMSH2 displays a p53 target gene, is induced by UVB radiation and is involved in NER pathways, studies have now been initiated to elucidate the physiological and pathophysiological role of MMR in malignant melanoma and nonmelanoma skin cancer development.