Allergic disorders (Allergy) such as asthma, eczema,hay fever, allergic rhinitis and food allergies are prevalent health problemsaround the world and caused by response of immune system to harmlessenvironmental antigens which is mainly mediated by TH2 response. In contrast toTH2 cells, TH1 cells produce pro inflammatory cytokines and are the majorplayer in immunity against infections, eliminating cancerous cells as well asautoimmune disorders (1).
Imbalance of these Th1/Th2 pathways is responsiblefor many immunological disorders including allergies, autoimmune disorders andhypersensitivity reactions, therefore manipulating and deviation one pathwaytoward the other is a promising strategy for management of many immune-relateddisorders, although there are some controversies(1-4).As the TH1 and TH2 cells down regulate each other, overactivation of one system, may exacerbate or alleviate symptoms. In this regard inverserelationship between atopic dermatitis and insulin-dependent diabetes mellitus aswell as different cancers reported(5). At the momentthere is controversy about the relationship between allergy and cancers. Some evidencessupported the protective role of Allergy against glioma(6), pancreaticcancer(7), andhematological malignancies(8), while a positiveassociation has been demonstrated between Allergy and lung cancer risk (9) and for Allergydigestive tract malignancies the results has been inconclusive (10).Two hypotheses suggestthe plausible mechanism for allergic conditions and tumor: immune surveillanceand the antigenic stimulation. The immune surveillance theory is frequentlyused to demonstrate the inverse relationships between atopic diseases and many cancers(8, 11, 12).
Atopic immune responsebeneficially eradicating cancer cells as by destroying tumorigenic exposures. It has been shown that T helper Type 2 (Th2)cytokines, which involve in the pathophysiology of atopic disorders, may contributein antitumor immunity(14). by attractingand activating eosinophils, macrophages, natural killer (NK) cells, and Type 2CD8+ T cells. IgE as the essential player ofallergic reactions has the pivotal role in response to allergens and promotingallergic symptoms but recently researchers have focused on its anti-cancerproperties and several studies demonstrated high tumoricidic effects of IgE (15,16).
On the other hand, the antigenic stimulationhypothesis suggests that overactive immune conditions stimulate chroniccellular inflammation, leading to DNA mutation in dividing cells and resulting totumor initiation and propagation(17). In addition,cytokines originated from Th2 cells such as interleukin4 (IL-4), IL-13 mediate somebiological effects, such as tumor proliferation, cell adhesion, cell survivaland metastasis (18,19). Studies published before 1985 provided evidences forreduced risk of cancer in allergic diseases (20).
Finding ofepidemiological studies since 1985 are more complex, implicating that theassociation might rely on both particular Allergy and specific organs.Inthis review, we discuss the existing data on the association between Allergy anddifferent type of cancers. A critical evaluation of the literature in this issueis important to clarify previous conflicting findings and to determine futureresearch directions.Hematological malignanciesAllergy has been assessed as protective factors forseveral cancers including childhood leukemia. Evaluation of 1842 childrenwith acute lymphoblastic leukemia (ALL) showed that a history of eczema associatedwith a significant reduction risk for cancer (odds ratio (OR)=0.7, 95% CI:0.5–0.
9)in a population-based case–control study in the USA(21). Also, historyof atopic dermatitis was related with significantly 50% lower risk for ALL andnot-significantly 20% decrement in the risk of acute myeloid leukemia (AML) (22). Controversy, astudy including 180 childhood ALL patients demonstrated no significant associationof childhood ALL with history of eczema (OR 1.1, 95% CI:0.6–2.0) (23).
Studies investigatingassociation in adult leukemia have mixed results. A non-significant risk of chroniclymphocytic leukemia(CLL) in adults with a history of eczema was announced inUSA population(24). Apopulation-based case-control study in Taiwan reported that any allergy and asthmawas related with an greater odds of childhood ALL (25).Specifically,in a meta-analysis performed in 2010 on childhood/adolescent ALL, the risks ofatopy/allergies, asthma, hay fever and eczema were 0.69, 0.79, 0.55, and 0.
74(95% CI: 0.54–0.89; 95% CI: 0.61–1.
02; 95% CI:0.46–0.55; and 95% CI:0.58–0.96)respectively(8). Recently, acohort population- based study in UK revealed that atopy is related with a 50 %lower risk of CLL (relative risk (RR)=0.5, 95 % CI:0.3–0.
8)(26).Hodgkin lymphoma (HL) ,malignancy of B-cell, is one of the most prevalent cancers in younger adults (27). It has been proposed that Allergy might be relatedwith an increased risk of HL, specifically among younger cases (28). Hollander et al found that history of allergicrhinitis was correlated with a non-significantly lower risk of HL (OR = 0.81, 95% CI:0.64 ,1.
03;P = 0.09)(29). The results with a lower incidence ofself-reported Allergy in HL patients are compatible to observations in studiesof Non-Hodgkin lymphoma (NHL