Picano et al. BMC Cancer 2012, 12:157 http://www.biomedcentral.com/1471-2407/12/157 Page 5 of 13 Table 2 Reports of brain cancer incidence in physicians, radiologists and interventionalists STUDY, YEAR Matanoski et al., 1975 [32] Wang JX et al., 1990 [33] METHODS Cohort study of mortality in 6,500 US male radiologists (years first worked 1920–1969) over a 50-year period FINDINGS Excess cancer risk among radiologists compared with other physicians Cohort study of Chinese diagnostic x-ray workers (1950 to 1985) Andersson M et al., 1991 [34] Cohort study of Danish radiation therapy workers Carozza et al., 2000 [35] Case–control study of occupation and glioma Andersen M et al., 1999 [36] Hardell et al., 2001 [37] Blettner et al., 2007 [38] Population-based study of occupation and cancer incidence (from the 1990s to 1980s) Case control study of 233 gliomas Case control study of German patients (age 30–59 years at diagnosis) with brain cancer in 2001–2003 Finkelstein et al., 1998 [39] Report of a case cluster (1990s) Roguin et al., 2012 [40] Report of a case cluster (2000s) new phenomenon with low levels of use compared with today. For most known carcinogens, identification of increased risk of solid tumors (particularly brain tumors) has required long follow-up periods of subjects with substantial exposure. For example, while the atomic bombs were dropped on Hiroshima and Nagasaki in August 1945, an ex- cess risk of solid tumors was reported in the survivors only in the 1960s, and no elevation in risk of brain tumors was noted for about 50 years [28]. Another important issue is that exposure from interventional cardiology is very asym- metrical, with the left side twice more exposed that the right side [4,13]. The risk, if it exists, is therefore likely to be more pronounced on the left side. Therefore, studies now at the starting blocks should enroll a well-characterized population of catheterization lab workers, record all (including non-fatal and non-malignant) cases of brain cancer and other non- brain head cancers, such as salivary glands, and assess the possible asymmetry of incidence (left- side cases being pos- sibly more frequent than right-sided cases) mirroring the asymmetry of dose exposure. Another potentially useful approach is the use of registry data. In some countries of Europe and the US, there are updated and reliable registries that can link occupational exposure with death and hospitalization records for a large number of individuals exposed many years ago [36,38]. Radiation exposure and vascular disease Systematic reviews of the published epidemiological lit- erature and cardiovascular disease [43,44], or reviews of studies of populations medically, occupationally or envir- onmentally exposed to relatively low-dose radiation [45- 47] concluded that there is a significant association Trend of excess cancer risk (standardized incidence ratio 1.2 for employment duration 10–14 years; 2.3 for 15–19 years) compared to non-radiation medical workers, not available for brain cancer Trend of excess cancer risk (standardized incidence ratio 1.09 with measured radiation dose < 5 mSv, and 2.23 with dose 5–50 mSv), not available for brain cancer Physicians at increased, albeit imprecise, risk of glioma (OR 3.5, CI 0.7- 17) Brain cancer increased among physicians in general; no breakdown by specialty Excess cancer risk of 6.0 in fluoroscopists Occupational exposure (physicians, nurses, radiographers) with OR 2.49 (0.74–8.38) for neurinoma, OR close to 1 for glioma and meningioma Brain cancer in two interventionalists 3 brain gliomas and 1 meningioma, left-sided, in 4 interventional cardiologists (although with substantial heterogeneity) between radi- ation exposure and circulatory disease, either cardiovas- cular or cerebrovascular. Vascular injury is a well- recognized cause of late radiation-therapy morbidity and this manifests as atherosclerosis in large vessels [7,8]. There is a significant increase in localized atherosclerosis after radiotherapy for head and neck cancer and this results in an excess risk of cardiovascular disease and stroke, which is increasingly evident with long follow-up (> 10 years) [43]. From current evidence, according to ICRP 2011 a judgement can be made regarding a thresh- old acute dose of about 0.5 Gy (or 500 mSv) for both cardiovascular disease and cerebrovascular disease [3] (Figure 3). On that basis, “0.5 Gy may lead to approxi- mately 1% of exposed individuals developing the disease in question, more than 10 years after exposure. This is in addition to the high natural incidence rate (circulatory disease accounts for 30–50% of all deaths in most devel- oped countries)." [3]. This dose threshold can be reached by an interventional cardiologist in his/her professional life as head dose and by a patient during some complex inter- ventional procedures [3]. Several biological mechanisms exist which might be responsible for linking radiation ex- posure to atherosclerosis. A relatively recent paradigm states that atherosclerosis is an inflammatory disease of the arteries that can lead to ischemia of the heart and brain, resulting in infarction. Chronic inflammation of the artery is initiated by endothelial dysfunction that may be caused, for example, by elevated low-density lipoproteins, and free radicals. The chronic inflammation results in altered function of macrophages and lymphocytes, whose activation causes the release of cytokines and growth