p53 mutations in basal cell carcinomas arising in routine users of sunscreens

Sun exposure histories were obtained from a series of patients age 35 or yo unger following diagnosis and removal of a basal cell carcinoma (BCC). The DNA was extracted from tumor biopsy samples derived from BCC of 10 patients who reported that they did not use sunscreens during youth (age 18 or youn ger) and 10 patients who routinely employed sunscreens during this age peri od. Exons 5-9 of the p53 gene were then amplified in three fragments from t hese samples using a nested polymerase chain reaction (PCR) approach and sc reened for mutations using an RNA heteroduplex assay. All PCR products disp laying evidence of a mutation were sequenced. It was found that 6 of the 10 patients who were not routine sunscreen users displayed mutations in these p53 exons, All of the mutations were located at dipyrimidine sites, five o f the six were C-->T transitions and one mutation was a tandem double mutat ion, consistent with a role for solar UVB in BCC formation. In contrast, on ly one p53 mutation was detected in the group of 10 patients who routinely employed sunscreens during childhood and adolescence, Hence, a significantl y (P = 0.029) lower level of p53 mutations was detected in the BCC obtained from sunscreen users compared with tumors derived from nonusers. These fin dings suggest that the mechanisms involved in the etiology of skin carcinog enesis differ in sunscreen users compared with people who did not routinely employ sunscreens, These data are also indicative of a protective effect a ssociated with sunscreen use against the formation of p53 mutations. It is possible that the patients who were diagnosed with BCC despite their use of sunscreens possessed a genetic susceptibility for skin cancer formation an d developed BCC through a p53-independent pathway, Alternatively, solar UVA wavelengths, that were generally not blocked by the suncare products emplo yed by the sunscreen users, may have played a significant role? in BCC deve lopment through induction of a mutation(s) in an oncogene and/or a tumor su ppressor gene, other than p53, for these patients.