Almost risk factor (OR=1.2, 95% CI: 0.8–2. 1)

Almost all epidemiological studies indicated that
people with a history of allergic disease have a greater risk of lung cancer (LC).
Five case–control studies among never-smoker reported risks of LC associated
with asthma to be 1.1–2.7 (88-91). Santillan and colleagues analyzed
results of five case–control studies and estimated (RR=1.8, 95% CI: 1.3– 2.3)(92). The analysis
of the data from studies, which controlled for smoking history gave a pooled
estimate of 1.7 (95% CI:1.3–2.2) (92). History of
asthma among nonsmokers and smokers cases were 1.6 and 1.7 respectively (88). Another study
expressed a strong association between asthma and with higher risk of LC only among
men (93). Another
population-based case–control study among Missouri woman found the asthma was a
non-significant risk factor (OR=1.2, 95% CI: 0.8–2. 1) in smokers and
significant risk factor (OR=2.7, 95% CI: 1.4–5.4) in non-smokers (89). This finding
is compatible with finding of study conducted among never-smoking women in five
city areas of the USA with risk of 1.7 (95% CI: 1.1–2.5) for history of asthma (90). A study in 98
female cases of small cell lung cancer (SCLC) and 204 controls in the USA
reported history of asthma related with statistically significant increased
risk of LC after adjustments (94). A study in
China reported the increased risk of asthma (OR=2.0; 95% CI: 0.9 to 4.2) among nonsmokers
even adjusting for smoking history (OR=2.1; 95% CI: 1.5 to 3.0) (91).

In a case–control study including 437 nonsmoking
cases and 437 controls was revealed no significant association among nonsmokers,
however a higher risk was found after adjusting for smoking history (OR=2.1, 95%
CI: 1.0–4.1)(95). In two studies
in Los Angeles were not observed any association between history of asthma and LC
after adjusting age and smoking history (96,
97). It have been
shown a reduced risk for LC among 217 case–control pairs women with asthma or
hay fever from the Californian nested case–control study (OR: 0.5, 95% CI:
0.3–1.0)(98). Similarly, prospective
cohort studies displayed a higher risk of LC among asthmatic patients. In a
prospective study on a Finnish twin cohort, the risk of LC-mortality was higher
in men with asthma (99). In a large
Finnish study covering 78000 participants, the risk of LC was increased (Standardized
Incidence Ratio (SIR) = 1.3 in men and SIR = 1.7 in women) among asthmatic
patients (100). In Swedish
patients which hospitalized for asthma (101), the SIR was
1.6 (95% CI: 1.5–1.7) during 8.5-years follow up.

Esophageal and gastric cancer

Inconclusive results were obtained from studies exploring
esophageal and gastric cancer risk factors. Ye et al. reported that
higher risk of esophageal and gastric cancers in asthmatic patients which may
be due to the more gastro-esophageal reflux in these patients (102). Several case-control
studies have reported inverse relationships between esophageal tumor and
history of allergy (103-105). Kallen et al. reported a
50% lower risk of stomach cancer mortality among asthmatics; but, cohort
studies reported no significant relationships(106).

Medullary thyroid carcinoma (MTC)

The association between a history of allergies and medullary
thyroid carcinoma (MTC) investigated in pooled analysis of 14 case-control
studies. Results of 48 cancer patients and 240 controls showed a twofold risk
for MTC in allergic disease. However, the positive association may as a result
of the release of vasoactive agents by the tumor leading allergic-like symptoms(107).

Bladder cancer (BlC)

An early case-control study expressed that a history
of atopic condition was associated to higher risk of BlC in men, but with a lower
risk in women(108). Other
case-control studies have demonstrated positive relationships of having history
of asthma and either urothelial tumor (109) or BlC(110). Interestingly,
risk of bladder tumor increased in asthmatics with the glutathione
S-transferase (GSTM1) or glutathione S-transferase (GSTT1) null genotypes. This
finding was speculated to be as a result of a lack of the detoxification of
reactive asthma medication intermediates by a deficiency of these enzymes(110). In cohort
studies was reported no significant associations (59) or advanced
risk for BlC in asthmatics patients only among men(100).



Rhabdomyosarcoma (RMS) is a scarce and high
malignant cancer of developing skeletal muscle which can happen anywhere in the
body. Lupo et al in a case-control study of 322 RMS cases and 322
controls found that allergies (OR = 0.60, 95% CI: 0.41–0.87) and hives (OR =
0.61, 95% CI: 0.38–0.97) were negatively related with childhood RMS(111).

Prostate cancer

Prostate cancer (PrC) is one of most frequent
malignancy in men and remains a main public health problem(112). There are several
studies exploring possible effect of systemic inflammation conditions on
prostate carcinogenesis. In a study was assessed single-nucleotide
polymorphisms (SNP) between patients with PrC and normal controls revealed that
4 genes (TLR1, TLR6, OAS1, and OAS2) participate in innate inflammation
pathways were associated to higher risk of Prc (113). Also, it has
been found that increased white blood cell count, as a marker of systemic
inflammation, was significantly associated with advance PrC risk(114). Results from
large-scale cohort study including 16,934 men which performed by Severi and
coworker revealed a small increment in prostate cancer risk in asthmatic
patients compared to controls (HR: 1.25; 95% CI: 1.05– 1.49) (115). Furthermore,
the risk was further elevated in cases allocating antiasthma medications such
as inhaled glucocorticoids, systemic glucocorticoids, and bronchodilators.

In a prospective questionnaire-based cohort study
reported that men with a history of asthma had a 30% low risk of lethal PrC(112). In contrast, Zhao
et al reported 86 of 1552 asthmatics were diagnosed PrC during follow-up(35). In the large nationwide
study, asthma was an independent risk factor for PrC and was associated to a
136% higher risk after adjustment for possible confounding factors. Also, there
was no direct relationship between history of glucocorticoids consumption and PrC
diagnosis. Glucocorticoids joined with mutated androgen receptors which may lead
to development and progression of androgen-independent PrC(116). Although,
there is inadequate document to establish this theory associated to prostate

In a large, population-based case-cohort study including
4124 cases with asthma and
8248 full-matched healthy control subjects, asthma was significantly associated
with prostate cancer (OR= 2.36; 95% CI: 1.22–4.57; P = 0.011) and its independent
risk factors were age and hypertension (117).

Head and neck cancer (HNC)

Head and neck cancer (HNC) (tumors of the oral
cavity, larynx oropharynx, and hypopharynx,) is the fifth most frequent cancer worldwide.
A meta-analysis of 14 studies showed an inverse association between allergy
symptoms and HNC risk (OR=0.76, 95 % (CI): 0.63–0.91) (118). In contrast,
cohort studies showed that higher serum IgE levels were related with an higher
risk of HNC (119). In a cohort study
with 14,849 participants subjects with positive tests for serum specific IgE for
inhalant allergens had higher risk of HNC (OR=1.74, 95 % CI:0.98–3.09). In other
cohort including 37747 subjects, high IgE levels was linked with an higher risk
of oral and pharyngeal cancer (OR=1.38, 95 % CI:1.04–1.84) (26).

Recently, Liao et al reported that elevated
serum total IgE levels was related with a significantly higher HNC (OR=1.71, 95
% CI: 1.21–2.42). Symptomatic allergy was related with a significantly lower
HNC risk (OR=0.56, 95 % CI: 0.43–0.73). Notably, asymptomatic atopic cases had
a higher risk of HNC than subjects with normal serum IgE level and no allergy

Squamous cell carcinoma (SCC) and early
onset basal cell carcinoma (BCC)

There are limited data about the contribution of
atopic and allergic conditions in the etiology of keratinocyte tumors. The
Finish Adult Twin Cohort study reported that females with a history of atopic
dermatitis prone to be more likely to affect a basal cell carcinoma (BCC), but
it was non-significant (OR=1.8, 95% CI:0.8–3.9) (121). A Danish
nationwide cohort study reported that increased risk of both squamous cell
carcinoma (SCC) and BCC among subjects who had a history of atopic dermatitis (122). Results from a
nested case–control study of skin cancer patients demonstrated that cases who
developed a new primary cutaneous SCC had higher prediagnostic IgE levels than
controls who did not (123). Similarly, a
higher risk of SCC was reported in asthmatics subjects compared with non-asthmatics
subjects(Table2) (124). Other studies
presented positive (124), negative (20,
61, 106, 125), and null association between BCC
and SCC and allergic condition (20,
125, 126). In a population-based
case–control study including 375 early onset BCC patients and 251 controls, as
well as 254 SCC patients and 432 controls, an overall inverse association was
reported between an allergic conditions and risks of early onset BCC but not
SCC. Interestingly, reduced risks of either early onset BCC or SCC related to
atopic history was observed only in women(127). Although,
almost all studies was discussed above had limited data about possible
modifying factors, for instance age at onset, type of allergy and its severity,
as well type of medications.

Cervical Cancer (CC)

Cervical cancer (CC) is a malignant cancer
of the cervix with nearly 277,000 new diagnosed cases and 266,000 deaths annually.
A case-control study among USA individuals reported that an odds of history of
any allergy was 0.7(95 % CI: 0.6 to 0.9) for squamous cell cervical cancer
(SCC). Also, they estimated the risk of CC related with SNPs in the chromosome
5 cytokine cluster genes(128).


Despite the hesitant results, the currently
available data from case-control and cohort studies indicate that Allergy is related
with a lower risk of cancer. Further research should focus on a more carefully
defined atopy status and manifestation of different atopic diseases, to advance
our understanding of the role that allergies might play in the risk of
developing cancer.  Prophylaxis hypothesis may be the more
probably explain the inverse association between Allergy and certain cancers.
Actually, relationship between cancer risk and allergy symptoms was more
commonly highlighted in malignancies of tissues or organs which interface the
external environment such as gasterointestinal cancers than others such as
breast and prostate cancers.

Many of discussed studies above collected data of
allergy symptoms retrospectively; so recall bias is plausible. Also, study
participants may mistake non-allergic symptoms and over-estimated the allergy
symptoms. Additionally, an ongoing chemoradiotherapy may influence the
manifestation of Allergy (129), which could
affect recall when subjects announcing history of atopic diseases.

The involvements of allergic inflammatory pathways
in growth and development of cancer provide an opportunity for further
evaluation and consideration. Moreover, establishment of the genetic mechanisms
behind the association between Allegy and cancers might allow a novel insight
to development of primary prevention and promising approach for effective
treatments for cancer patients.


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