Allergic strategy for management of many immune-associated disorders,

Allergic disorders (Allergy)
such as asthma, eczema, hay fever, allergic rhinitis and food allergies are common
health problems around the world and as a result of immune system response to innocuous
environmental antigens which is mainly mediated by TH2 response. In contrast to
TH2 cells, TH1 cells produce pro inflammatory cytokines and are the major
player in immunity against infections, eliminating cancerous cells as well as
autoimmune disorders (1). Imbalance of
these Th1/Th2 pathways is responsible for multiple immunological disorders
including allergies, autoimmune disorders and hypersensitivity reactions, consequently
manipulating and deviation one pathway toward the other is a promising strategy
for management of many immune-associated disorders, although there are some
controversies (1-4).

As the TH1 and TH2
cells down regulate each other, over activation of one system, may exacerbate or
relieve symptoms. In this regard inverse relationship between atopic dermatitis
(AD) and insulin-dependent diabetes mellitus as well as  different cancers reported (5). At the moment
there is controversy about the relationship between allergy and cancers. Some evidences
supported the protective role of Allergy against glioma (GM) (6), pancreatic
cancer (PC) (7), and
hematological malignancies (8), while a positive
association has been demonstrated between Allergy and lung cancer (LC) risk (9) and for Allergy
and gastrointestinal  (GI) cancers the
results has been inconclusive (10).

Two hypotheses suggest
the plausible mechanism for allergic conditions and tumor: immune surveillance
and the antigenic stimulation. The immune surveillance theory is frequently
used to demonstrate the inverse relationships between atopic diseases and many tumors
(8,
11, 12). It has been shown that T helper
Type 2 (Th2) cytokines, which participate in the pathophysiology of atopic disorders,
may contribute in antitumor immunity(13) by attracting
and activating eosinophils, macrophages, natural killer (NK) cells, and Type 2
CD8+ T cells. IgE as the essential player of
allergic reactions has the pivotal role in response to allergens and up-grading
allergic symptoms but recently researchers have concerned on its anti-cancer
properties and several studies demonstrated high tumoricidic effects of IgE (14,
15).

On the other hand, the
antigenic induction hypothesis suggests that overactive immune conditions stimulate
chronic cellular inflammation, causing DNA mutation in dividing cells and consequently
tumor initiation and propagation (16). In addition,
cytokines originated from Th2 cells such as interleukin 4 (IL-4), and IL-13 mediate
some biological effects, such as tumor proliferation, cell adhesion, cell
survival and lymph node-metastasis (17,
18).

Studies published
before 1985 provided evidences for reduced risk of cancer in allergic diseases (19). Finding of
epidemiological studies since 1980s are more complicated, implicating that the
association might rely on both particular Allergy and specific organs.
In
this review, we discuss the existing data on the association between Allergy and
different type of cancers. A critical evaluation of the literature in this matter
is essential to clarify previous controversial findings and to determine future
research directions.

Hematological
malignancies

Allergy has been
assessed as protective factors for several cancers including childhood leukemia. Evaluation
of 1842 children with acute lymphoblastic leukemia (ALL) disclosed that a
history of eczema correlated with a significant reduced risk for cancer (odds
ratio (OR)=0.7, 95% CI:0.5 to 0.9) in a case–control study in the USA(20). Also, history
of AD was related with significantly 50% lower risk for ALL and not-significantly
20% decrement in the risk of acute myeloid leukemia (AML) (21). Controversy, a
study including 180 childhood ALL patients in Taiwan demonstrated no
significant association of childhood ALL with history of eczema (OR 1.1, 95% CI:0.6
to 2.0) (22). Studies evaluating
association in adult leukemia have mixed results. A non-significant risk of chronic
lymphocytic leukemia (CLL) in adults with a history of eczema was announced in
USA population (23). A case-control
record and population-based study reported that any allergy and asthma was
related with an greater odds of childhood ALL (24).
Specifically,
in a meta-analysis performed in 2010 on childhood/adolescent ALL, the risks of
atopy/allergies, asthma, hay fever and eczema were 0.7, 0.8, 0.5, and 0.7 (95%
CI: 0.5 to 0. 9; 95% CI: 0.6 to 1.0; 95% CI:0.4 to 0.5; and 95% CI:0.6 to 0.9)
respectively (8). Recently, a
cohort population- based study in UK revealed that atopy is linked with a 50 %
lower risk of CLL (relative risk (RR)=0.5, 95 % CI: 0.3 to 0.8)(25).

Hodgkin lymphoma (HL) ,
malignancy of B-cell, is one of the most prevalent cancers in younger adults (26). It has been proposed
that Allergy might be related with an increased risk of HL, particularly in
younger cases (27). It has reported
that history of allergic rhinitis was correlated with a non-significantly lower
risk of HL (OR = 0.8, 95 % CI: 0.6 to 1.0; P = 0.09)(28). Similarly, self-reported
of hay fever, was associated with a 14% lower risk of non-Hodgkin (NHL) in a
large population-based study (29).

Breast cancer

Breast cancer (BC) is
the second most frequent cause of cancer related mortality among women
worldwide. In 1985s, a study reported no association between BC risk and hay
fever, but the risk of BC was rather decreased in women with history of hives
or other allergies (19). But in other
study, a history of allergies or hay fever was related with a 20% lower risk of
BC (95 % CI: 0.7 to 0.9) (30). Also, among young
American women, an allergic condition was associated with a low risk of BC (31). Other several
studies of allergies and BC risk represented no association, although may not
have had enough power to evaluate this association (32-34). Case control studies evaluating relationships
of allergy and BCs was shown in table1.

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