p53 codon 72 Pro homozygosity increases the risk of cutaneous melanoma in individuals with dark skin complexion and among noncarriers of melanocortin 1 receptor red hair variants

Abstract

Background: p53 has a common polymorphism at amino acid 72, encoding either arginine or proline. p53Arg and p53Pro exhibit differences in various biological activities, such as cell-cycle arrest and induction of apoptosis. Numerous epidemiological studies have examined the role of this polymorphism in several human malignancies, including cutaneous cancers, with contradictory results.

Objectives: To investigate the germline frequency of p53 codon 72 polymorphism in malignant melanoma in a Mediterranean population, and to examine possible associations with various clinicopathological factors.

Methods: In this hospital-based case-control study we used allele-specific polymerase chain reaction for p53 codon 72 genotyping in blood specimens from 107 Greek patients with sporadic cutaneous melanoma and 145 healthy controls.

Results: After adjustment for age, sex and phototype the Pro/Pro genotype was associated with increased risk for cutaneous melanoma compared with the Arg/Arg genotype (adjusted odds ratio, OR 3.17, 95% confidence interval, CI 1.03-9.78). This correlation was more pronounced in subjects with phototypes III or IV (adjusted OR 9.56, 95% CI 1.56-58.46), dark skin (adjusted OR 10.96, 95% CI 1.64-73.28), dark eyes (adjusted OR 8.86, 95% CI 1.69-46.52) and dark hair (adjusted OR 3.17, 95% CI 1.01-9.95), and among noncarriers of melanocortin 1 receptor gene (MC1R) red hair polymorphisms (adjusted OR 2.99, 95% CI 1.02-8.78).

Conclusions: p53 codon 72 Pro/Pro genotype could be a risk factor for the development of melanoma in the Greek population, especially in subgroups with darker skin pigmentation, as well as among noncarriers of the MC1R red hair polymorphic variants.