Picano et al. BMC Cancer 2012, 12:157 http://www.biomedcentral.com/1471-2407/12/157 heads due to a oncogenic “bystander radiation effect”, probably linked to soluble factors released by irradiated cells [25]. In addition to the absorbed dose and type of ra- diation, the probability of stochastic effects varies depend- ing on the organ or tissue irradiated. To calculate the effective dose, the individual organ dose values (equivalent doses) are multiplied by the respective dimensionless tis- sue weighing factor. In radiation protection, the tissue weighting factor is a factor weighting the equivalent dose in a particular tissue or organ in terms of its relative con- tribution to the total deleterious effects resulting from uni- form irradiation of the whole body. In other words, the higher this factor, the more radiosensitive the tissue. The ICRP has offered recommended tissue weighting factors in three reports, their Publication 26 (1977) [26], Publication 60 (1991) and the most recent Publication 103 (2007) [7]. The key changes introduced in ICRP Publication 103 are a 140% increase in breast risk factor from 0.05 to 0.12 (a value similar to colon, lung, stomach and red bone mar- row, all considered highly radiosensitive tissues) and a de- crease in gonad weighting from 0.20 to 0.08 (Table 1). In 2007, brain tissue was given more weight and received 0.01 of weighting factor, whereas it was clustered among the remainder (with 14 other tissues) in the 1991 version. A similar trend was shown for the salivary glands, which may also suffer from high head irradiation in catheterization laboratory workers. Shifting from a radioprotection to an oncology perspec- tive, ionizing radiation is one of the few established causes of neural tumors. The sensitivity of the brain tissues to Table 1 Tissue weighting factors from ICRP (2007 vs 1991 and 1997) ICRP 268 (1977) ICRP 60 (1991) ICRP 1037 (2007 Bladder Bone Brain Breasts Colon Esophagus Liver Lower large intestine Lungs Ovaries/testes Red marrow Remainder tissues Salivary glands Skin Stomach Thyroid Adapted from refs 7, 26 and 27. _ _ _ 0.03 _ _ _ 0.15 _ _ _ _ _ _ _ _ _ _ _ _ 0.12 0.25 0.12 0.30 _ _ _ _ _ _ _ _ _ 0.05 0.01 _ _ _ 0.05 _ _ _ 0.05 0.05 0.12 0.12 0.20 0.12 0.05 _ _ _ 0.01 0.12 0.05 _ _ _ 0.04 0.01 0.01 0.12 0.12 0.04 0.04 0.12 0.08 0.12 0.12 0.01 0.01 0.12 0.04 Page 4 of 13 develop benign and malignant tumors after diagnostic X- rays was shown in several case–control studies, four of them from dental exposures, and with relative risks ran- ging from 1.6 to 10 [27]. Studies of the incidence of ner- vous system tumors in atomic bomb survivors concluded that exposure to radiation doses of less than 1 Sv is asso- ciated with an increased incidence of nervous system tumors [28]. A review of cohort mortality studies among workers exposed to ionizing radiation in U.S. nuclear pro- grams was reported in 1991 and reappraised in 2001 [29], with 3.8 person-years of observation among 140,000 white male workers. The increased risk of brain tumor was highly consistent, persistent, and stable, on the order of magnitude of 15–30%. As a consequence of these data, policy makers have identified brain cancer as a "specified" cancer potentially related to occupational exposures under the Energy Employees Occupational Illness Compensation Program Act [30]. Cosmic radiation can also probably pro- voke brain tumors. In a large German cohort of 6,017 cockpit and 20,757 cabin crew members, Zeeb et al. reported an increased fatal brain tumor risk among cock- pit (not cabin) crew, with the relative risks of 1, 2.49 and 3.56 for workers with 10–20 years, 20–30 years, and > 30 years duration of employment, respectively [31]. Epidemiologic evidence for radiation-induced brain can- cer in fluoroscopists is suggestive, but by no means conclu- sive (Table 2) [32-40]. One study [32] found that the death rate from brain cancer in radiologists was almost three times that of other medical specialists who did not use radi- ation. A case–control study [37] of 233 patients with brain tumors reported that work as a physician with use of fluor- oscopy increased the risk of developing a brain tumor, with an odds ratio of 6.0 (95% CI, 0.62–57.7), although there were only three such individuals among the 233 cases. An- other case–control study [35] of 476 individuals diagnosed with glioma also observed an increased risk in physicians and surgeons (odds ratio, 3.5; 95% CI, 0.7–17.6). However, such studies cannot exclude other biologic agents and che- micals unrelated to radiation as causative, and other case– control studies failed to identify a significant risk of brain tumors as a result of a generic exposure to medical ionizing radiation [38]. Essentially, no data are available on the con- temporary population of invasive fluoroscopists, whose level and pattern of head exposure is unprecedented, although some anecdotal clusters of brain cancer have been recently described [39,40]. Of particular interest, the most recent de- scription of three brain gliomas and one meningioma in interventional cardiologists all involved the left side, known to be more exposed than the right side, although no brain radiation dose was provided for any of these cases [40]. In general, we should consider some important methodo- logical aspects: 1) timing of studies; 2) sample size; 3) chan- ging levels of exposure [41,42]. Most studies were conducted at a time when interventional cardiology was still a relatively