Comparative Effects of Sunscreens Alone vs Sunscreens Plus DNA Repair Enzymes in Patients With Actinic Keratosis: Clinical and Molecular Findings from a 6-Month, Randomized, Clinical Study
September 2015 | Volume 14 | Issue 9 | Original Article | 986 | Copyright © September 2015
Mauro Carducci MD,a Paolo Sergio Pavone MD,b Giuseppe De Marco MD,a Silvia Lovati MD,b
Velimir Altabas MD,d Karmela Altabas MD,d and Enzo Emanuele MDc
aCentro Ortopedico di Quadrante, Omegna (VB), Italy
bErba-Renaldi Hospital, Menaggio (CO), Italy
cLiving Research s.a.s., I-27038, Robbio (PV), Italy
dUniversity Hospital Centre “Sestre milosrdnice,” Zagreb, Croatia
Abstract
Recent experimental irradiation studies have shown that the addition of DNA repair enzymes (photolyase and endonuclease) to traditional sunscreens may reduce ultraviolet radiation (UVR)-induced molecular damage to the skin to a greater extent than sunscreens alone. In this 6-month, randomized, clinical study, we sought to compare the clinical and molecular effects of sunscreens plus DNA repair enzymes vs. those of traditional sunscreens alone in patients with actinic keratosis (AK). A total of 28 AK patients were randomized to topically apply sunscreens plus DNA repair enzymes (enzyme group; n = 14) or sunscreens alone (sunscreen group; n = 14) for 6 months. The main outcome measures included 1) hyperkeratosis, 2) field cancerization (as measured by fluorescence diagnostics using methylaminolaevulinate), and 3) levels of cyclobutane pyrimidine dimers (CPDs) in skin biopsies. Both regimens produced a significant reduction of hyperkeratosis at 6 months, with no difference between the two groups. Field cancerization was significantly reduced by both regimens, but the decrease observed in the enzyme group was significantly more pronounced than in the sunscreen group (
P < 0.001). At 6 months, CPDs decreased by 61% in the enzyme group and by 35% in the sunscreen group compared with baseline values (
P < 0.001). These findings indicate that, despite a similar effect on hyperkeratosis, the addition of DNA repair enzymes to sunscreens was more effective in reducing field cancerization and CPDs than sunscreens alone. Taken together, our findings indicate that sunscreens plus DNA repair enzymes may be superior to traditional sunscreens alone in reducing field cancerization and UVR-associated molecular signatures (CPDs) in AK patients, potentially preventing malignant transformation into invasive squamous cell carcinoma in a more efficient manner.
J Drugs Dermatol. 2015;14(9):986-990.
INTRODUCTION
Non-melanoma skin cancer is a complex multistep disease that arises from accumulating genetic alterations of critical cell regulatory genes associated with a high degree of genomic instability in skin keratinocytes.1 Chronic exposure to ultraviolet radiation (UVR) in fair-skinned patients is universally recognized as the primary risk factor for the development of skin cancers, with these lesions occurring primarily on chronically sun-exposed skin areas (e.g., the head, face, and back of the hands).2,3 DNA in keratinocytes readily absorbs UVR and is highly susceptible to forming photoproducts, mainly in the form of cyclobutane pyrimidine dimers (CPDs). CPDs have been shown to induce bulky lesions in the structure of DNA, ultimately representing the primary cause of mutations in skin tumorigenesis.4,5
Actinic keratoses (AKs) are common premalignant intraepidermal lesions that are generally considered as precursors of squamous cell carcinoma (SCC).6,7 The presence of AKs may be regarded as a major warning sign that subclinical UVR-induced photodamage has accumulated over time.8 The subclinical field changes suggest the widespread presence of DNA-damaged cells which are called field cancerization.9 The term field cancerization is therefore used to indicate the presence of extensive skin areas with multiple precancerous lesions (clinically visible AKs and subclinical AKs characterized by histologic atypia) that have a potential of developing into SCC, indicating the presence of a spectrum of malignant progression.10 Notably, it has been suggested that the number of subclinical AKs in chronically photodamaged areas can exceed the number of clinically visible AKs by ten-fold.11
The clinical usefulness of regular use of sunscreens for preventing the development of AKs and possibly reducing the risk of skin cancer in the long-term has been initially demonstrated in the seminal work by Thompson et al.12 Subsequently, several independent investigators have confirmed that sunscreens
