Allergy and cancer: a biological and epidemiological rebus

The debate on the relation between allergy and cancer is not recent (1, 2). The increased burden of allergic diseases in the last decades (3–6) and the new discoveries about the immunology of cancer (7–9), enhanced the interest on such relationship. Theoretically, two general hypotheses may be advanced: either tumor immunosurveillance may operate more efficiently in those individuals who have allergies or the alterations of the immunologic system can enhance inflammatory response and favor the tumor onset. Under the epidemiological point of view, the examination of the relation between allergic-related disorders and cancer development is still needed. To know the direction of a possible association between the two phenomena might contribute to cancer prevention. However, any epidemiological conclusion can’t leave out the complex results of basic science and it must follow the rule of biological plausibility. The concept of multi-stage carcinogenesis implies that cancer prevention is feasible, at each stage, with different strategies. Defense mechanisms existing in different stages of carcinogenesis (e.g. detoxification of metabolites coming from environmental carcinogens, trapping or decomposition of reactive oxygen species, DNA repair enzymes, natural inhibitors of proliferating initiated cells, etc.) have been recently emphasized (10). The immune system may be the last line of defense against cancer development. According to the most recent point of view about cancer immunology (8), the key issue is whether recognition of tumor antigens by the immune system leads to activation (i.e. surveillance) or tolerance. These apparently disparate views can be reconciled into a unified hypothesis in which tumors must develop specific mechanisms for locally inhibiting the activation of innate and adaptive immunity in order to progress successfully through invasive and metastatic stages (8). At this regard, observations in human populations have been limited; thus, epidemiological approaches may be the most suitable way to assess the relation between host immunological status and future development of cancer in humans (10). The papers from Wang and Diepgen (11) and from Lindelof et al. (12) represent a consistent basis for this open discussion. The former is a comprehensive review of the epidemiological studies after 1985. Sixty-six studies have been analyzed for more than eight different sites of tumor. The general conclusion is that Despite the mixed results.allergy is associated with a reduced risk for cancer . It stands especially for colon cancer, pancreatic cancer, childhood leukemia and brain tumors. Conversely, the only tumor positively associated with allergy is lung cancer. As a consequence, if cancer is also an organ-specific diseases with a specific natural history, the role of immunity may be different for different cancer sites. In the case of lung cancer, for which particularly asthmatic subjects show an elevated risk, mechanisms related to the interaction between environmental and host factors, on one site, and the airways, on the other site (airway obstruction, remodeling, wall damages, etc.), might explain the epidemiological findings. For cancers in other sites, especially if related to microbiological agents, for which a reduced or a non-significant risk has been reported, a protective effect of enhanced immunity system in allergic subjects might be taken into consideration. However, as the two Authors point out, many methodological problems or possible sources of bias have to be considered: study designs (many case–control instead of cohort-prospective studies), recall bias, small number of subjects, variability in the definition of allergy, lack of an objective measure of allergy, impossibility to analyze the role of confounders or effect modifiers. L. Carrozzi, G. Viegi Pulmonary Environmental Epidemiology Unit – CNR Institute of Clinical Physiology, Pisa; Cardiopulmonary Department – University Hospital of Pisa, Pisa, Italy