| BACKGROUND: The efficacy of topical treatment with coal tar in patients diagnosed with psoriasis or eczema has been well established. However, coal tars contain numerous polycyclic aromatic hydrocarbons (PAHs), e.g. benzo[a]pyrene, which are transformed by the cytochrome P450 system into reactive metabolites capable of interaction with DNA. Concern has been raised about the carcinogenicity of coal tar treatment in the dermatological practice. The percutaneous absorption of mutagens from patients receiving coal tar has been demonstrated in blood and urine. An increased risk of non-melanoma skin cancer in coal tar treated patients (with and without exposure to artificial ultraviolet radiation) has been found in several studies. An increased risk of non-skin cancers related to coal tar treatment has never been established. In animal studies and human occupational studies, the carcinogenicity of coal tar has clearly been demonstrated. The reported malignancies related to occupational exposure appeared after chronic exposure, whereas the use of coal tar in dermatological diseases is usually limited to relatively short periods. On the other hand the exposure to coal tar in a therapeutical setting is much higher compared to occupational exposure. Because of the increased awareness of potential carcinogenic and mutagenic environmental influences a reluctance to use tar has evolved in some European countries. The use of tar in cosmetics is prohibited in the European Union since 1998. Treatment of skin disorders by coal tar, however, is effective and probably safer than its immunosuppressive topical and oral alternatives and should therefore not be banned before proper risk assessment. PURPOSE OF THE STUDY: To investigate whether patients with psoriasis or eczema treated with coal tar have an increased risk of skin malignancies (excl. basal cell carcinoma) and non-skin cancers compared to (1) the general population and (2) patients with psoriasis or eczema treated differently. PLAN OF INVESTIGATION: A historical cohort study will be conducted. A cohort of 10,000 patients with psoriasis or eczema will be identified (50% of the patient treated with coal tar and 50% treated differently). All patients treated in one of 3 University Hospitals (University Medical Center Nijmegen, University Hospital Groningen and Academic Hospital Maastricht) in the Eastern part of the Netherlands in the period 1960-1990 will be included. After identifying the patients, their addresses will be checked and updated if necessary by means of Dutch patient associations, computerized telephone directories, municipality administrations and general practitioner records. All patients will receive an invitation letter from the Dermatology Department where they were treated and will be asked to participate in the study by filling out an enclosed questionnaire on demographic factors, smoking history, diet (incl. alcohol), occupational history, sunbathing, occurrence of cancer and other chronic diseases, occurrence of skin diseases and its treatment. After written permission of the patients, occurrence of cancer will be verified by medical records (for patients diagnosed before 1989) and by linkage to the Netherlands Cancer Registry (for patients diagnosed after 1989 because the Netherlands Cancer Registry is considered to be complete since 1989). The study outcome will be cancer incidence. Cancer incidence in coal tar treated patients will be compared to (1) cancer incidence in the general population and to (2) patients treated differently. The power will be sufficient to detect an increased overall cancer risk in coal tar treated male and female patients by a factor 1.3. Possible results of this project include estimation of treatment specific (especially coal tar treatment) relative and absolute cancer risks in patients with psoriasis or eczema. If coal tar exposure in the therapeutical setting is associated with an increased risk of (non-skin) cancer, a treatment policy has to be formulated regarding the use of coal tar in the dermatological practice and implemented (inter)nationally. |
