ArticlesDaily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial
Introduction
The incidence of skin cancer in white populations is similar to the overall incidence of all other cancers, and continues to increase.1 Although avoidance of long or intense sun exposure through shelter or protective clothing is the mainstay of skin-cancer prevention,2 amounts of sun exposure remain high in western populations.3 Supplementary measures to lessen the harmful effects of sun exposure have, therefore, been sought, and for many years the application of sunscreen to sun-exposed skin has been advocated as one such measure. Although the short-term efficacy of sunscreen in the prevention of sunburn is undisputed, there is no evidence that long-term use of sunscreen prevents skin cancer. Some evidence comes from two trials of sunscreen in relation to benign solar keratoses. A trial of daily sunscreen application for 7 months among 588 people with solar keratoses in Australia suggested that the incidence of further keratoses was decreased by the regular use of sunscreen,4 as did the follow-up of 50 volunteer patients of a US dermatology clinic who were randomly assigned daily application of sunscreen or sunscreen base.5
Antioxidant micronutrients such as betacarotene may also provide protection against skin cancer by lessening free-radical-induced damage to DNA in skin cells after solar ultraviolet exposure or by affecting cellular differentiation and proliferation after conversion to retinol.6, 7 Betacarotene has been shown to decrease the number of skin tumours in mice exposed to ultraviolet radiation.8, 9 Previous large randomised placebo-controlled trials have investigated the effects of betacarotene on the primary prevention of various other cancers10, 11 but non-melanoma skin cancers were excluded. One trial of betacarotene supplementation in the secondary prevention of skin cancer showed no difference in incidence of non-melanoma skin cancer between people receiving 50 mg betacarotene or placebo daily after 5 years.12
The Nambour Skin Cancer Prevention Trial aimed to investigate the effectiveness of daily sunscreen application and of dietary betacarotene supplements in reducing the incidence of basal-cell carcinoma and of squamous-cell carcinoma in 1621 members of a typical Queensland community over a period of 4·5 years. We postulated that primary prevention of skin cancer was possible if adults reduced their daily solar ultraviolet exposure by application of sunscreen to commonly sun-exposed sites on the head, neck, arms, and hands, or if the carcinogenic process were opposed by betacarotene supplementation. Our hypothesis was that each intervention would decrease the incidence of new basal-cell carcinomas or squamous-cell carcinomas and would lower the overall number of skin cancers of each type treated in the intervention period.
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Participants
Study participants were originally randomly chosen residents of Nambour, a township in southeast Queensland (latitude 26°S), who were aged between 20 and 69 years when they took part in a skin-cancer survey in 1986.13 To be eligible for the current study, the original survey participants had to attend a second survey in 1992, undergo a complete skin examination by a dermatologist with removal of all diagnosed skin cancers, and give written consent to take part in this randomised trial until
Design
In a 2 by 2 factorial design, individuals were assigned, before the 1992 survey, to one of four treatment groups by generation of a random assignment sequence. At the 1992 baseline survey, those eligible were allocated to one of the four groups: daily use of sun protection factor 15 plus broad-spectrum sunscreen and taking one 30 mg betacarotene tablet each day; daily sunscreen and placebo tablets; betacarotene only; and placebo only. Participants not assigned to daily application of sunscreen
Statistical methods
The primary endpoint for the intention-to-treat analysis was incidence of skin cancer (person-time based) calculated as the number of people treated for new basal-cell carcinoma or new squamous-cell carcinoma between Jan 1, 1993, and Aug 31, 1996, divided by the person-years accumulated between these dates and expressed per 100 000 person-years. Tumour rates were calculated similarly, with the total number of tumours occurring for all participants as numerator. With 1600 participants and a loss
Results
Of 1647 eligible residents of Nambour who attended the baseline skin-cancer survey in 1992, 1621 gave signed consent to participate in the trial and were allocated treatments (figure). 436 (27%) of these people had previously had skin cancer, and at baseline skin cancer was diagnosed for the first time in a further four people. Treatment allocation was unrelated to baseline characteristics of participants including age, sex, skin type, sun exposure, presence of skin damage caused by the sun,
Discussion
The rates of new skin cancers in this study are higher than the rates of basal-cell carcinoma (788 per 100 000) and squamous-cell carcinoma (321 per 100 000) reported for Australians overall,17 despite the use of potentially preventive agents. This finding reflects not only the higher baseline level of skin cancers in residents of subtropical Queensland, but also more intensive monitoring of new diagnoses of skin cancer than has been possible in previous surveys. Outcomes for basal-cell
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