THE POSSIBLE ROLE OF RADIOFREQUENCY RADIATION IN THE DEVELOPMENT OF UVEAL MELANOMA.

Stang, A.; Anastassiou, G.; Ahrens, W.; Bromen, K.; Bornfeld, N.; Jockel, K-H.

Inst. for Medical Informatics, Biometry and Epidemiology, Medical Faculty, Univ. of Essen, Hufelandstrasse 55, 45122 Essen, Germany (RR/A.S., W.A., K.B., K-H.J.); Div. of Ophthalmology, Medical Faculty, Univ. of Essen, Hufelandstrasse 55, 45122 Essen, Germany (G.A., N.B.)

Uveal melanoma (UM) is a rare form of intraocular malignancy with a European incidence rate of up to 1 per 100,000 person-yr. The possible role of radiofrequency (RF) electromagnetic field exposure in the development of UV was examined as part of a population-based case-control study conducted between 1994 and 1997 on occupational risk factors for 8 rare malignancies: (1) UM, (2) mycosis fungoides, (3) cancer of the small intestine, (4) bone cancer, (5) bile duct cancer, (6) male breast cancer, (7) thymoma, and (8) testicular cancer. During the field phase of the study, a hospital-based case-control study of risk factors for UM was started at the Div. of Ophthalmology, Univ. of Essen, Germany, using the same protocol and personnel as the population-based study. A total of 118 male and female cases of UM from both studies were interviewed. Controls in the population-based study were drawn from lists of local residents and controls in the hospital-based study were drawn from patients hospitalized for other ophthalmologic problems such as retinal detachment, macular degeneration, and retinal vascular occlusion. After matching for age (5-yr intervals), sex, and region of residence and excluding controls that only matched other rare cancer types, 475 interviewed controls were included in the analysis. Topics covered in the interviews included medical history, phenotypic characteristics, lifestyle factors, a detailed lifetime occupational history, and occupational sources of electromagnetic radiation. These sources included working close to high-voltage electric lines, electrical machinery, complex electrical environments (such as control rooms or computer rooms), video display units (VDUs), radar units, and other RF radiation sources. Occupational exposure to RF radiation devices was assessed by asking the subjects whether they ever used radio sets, mobile phones, or similar devices at their workplace for at least several hr per workday. Subjects who answered yes were asked about the starting and ending years of exposure and details of the RF radiation source and how the RF source was carried in the case of mobile communication devices. The reference date for the exposure was the date of UM diagnosis (cases), date of first contact letter (population controls), and date of diagnosis (hospital controls). Only exposures that occurred before the reference date were included in the analysis. In pooled analysis (combining subjects in the population- and hospital-based studies), 18 UM cases and 55 controls reported being exposed to RF sources. The RF radiation exposures were grouped into 4 categories by an investigator blinded to the subjects' case-control status: (1) exposed only to radio receivers that do not transmit RF radiation (unexposed); (2) exposed to walkie-talkies and radio sets; (3) possibly exposed to mobile phones; and (4) probably or definitely exposed to mobile phones. Conditional logistic regression techniques were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Among the UM patients, the tumors involved the choroid (98%), iris (1%), and unknown parts of the uveal tract (1%). The highest EMF exposure prevalence was seen for electrical machines and VDUs. Neither of these exposures were significantly associated with UM risk. Among the RF radiation sources, only exposure to radio sets or mobile phones was significantly and consistently associated with an increased risk of UM, the others being close to unity or uninformative due to low exposure prevalence (radar units). The ORs in the pooled analysis, the population-based, and hospital-based studies (considered separately) for any exposure to radio sets were 3.3 (CI 1.2-9.2), 4.6 (CI 1.0-19.2), and 1.8 (1.1-484.4). When the groups were limited to those exposed 5 or more yr before the reference date, ORs were not increased (ORs of 3.3 (CI 1.2-9.2), 4.5 (CI 1.0-17.5), and 2.0 (CI 0.3-15.8), respectively). For probable/certain mobile phone exposure, the ORs were 4.2 (CI 1.2-14.5), 1.6 (CI 0.0-16.5), and 10.1 (CI 0.9-8.1), respectively. Again, risk estimates were not substantially increased by considering only subjects exposed more than 5 yr before the reference date or for 3 or more yr duration. Subjects probably or certainly exposed to mobile phones typically worked in the service sector (real estate agents, tax consultants, or sales representatives) and had a median year in which they started exposure of 1993, considerably later than when subjects started exposure to radio sets (median year of 1975). This reflected the more recent widespread introduction of mobile phones to the German market. The number of exposed subjects was generally quite low: overall, only 46 controls (9.7%) and 16 cases (13.6%) were occupationally exposed to any kind of RF radiation source for 6 mo or more. Only 1 female case and 1 female control (both in the hospital-based study) reported being exposed to any RF radiation at their workplace, and they were rated as probably or certainly exposed to mobile phones. Adjusting for socioeconomic status, measured by years of education, did not significantly alter the results. Light iris color (blue, gray, green, or light brown) vs. dark iris color (dark brown) and light hair color (red or blonde) at age 20 yr were significantly associated with an increased UM risk, the pooled ORs being 2.9 (CI 1.5-5.6) and 1.4 (CI 0.9-2.3), respectively. However, controlling for iris and hair color did not significantly affect the results. The authors noted that this is the first study that has described an association between RF radiation exposure and UM, and that the association between EMF exposure and UM is limited to RF radiation. The results of this study, however, do not establish any cause-effect relation between RF radiation and UM because of substantial limitations such as the small size of the exposed population, possible recall bias, and nonspecific questions about exposure to RF sources producing a less than precise exposure assessment. Nonetheless, the authors speculate on a possible mechanistic explanation for the observed association of RF radiation with UM, postulating that RF radiation decreases synthesis of ocular melatonin, thereby reducing the antiproliferative effect of melatonin on growth of UM cells. (22 Refs). [Copyright 2001, Information Ventures, Inc.]

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