Risk of Squamous Cell Carcinoma of the Skin in Relation to IgE: a Nested Case–Control Study

Abstract

Background Individuals diagnosed with non-melanoma skin cancer have a high risk of developing a second skin cancer diagnosis. We assessed whether a marker of immune function related to atopic allergy, IgE, was associated with diagnosis of subsequent squamous cell carcinoma (SCC) of the skin in patients with a previous skin cancer enrolled in a skin cancer prevention trial. Methods One hundred twelve cases with a repeat skin cancer diagnosis were compared to 227 controls, matched on age, sex, and study center. Total, respiratory, and food-specific IgE were measured in the baseline or year one (prior to diagnosis) sera samples for each subject. Results IgE levels were higher in cases with a second SCC than controls (comparing the highest quartile to the lowest, ORtotal IgE=1.44; 95% CI:0.73–2.85; ORrespiratory IgE =2.43; 95% CI:1.16–5.06; ORfood IgE =2.53; 95%CI:1.19–5.35). The association between respiratory IgE and subsequent skin cancer was strongest among individuals with a tendency to sunburn (ORrespiratory IgE =3.82; 95%CI: 1.05–13.88) compared with those with a tendency to tan (ORrespiratory IgE = 0.95; 95%CI:0.20–4.76). Among 25 subjects with repeat IgE measurements taken over several years, IgE levels were remarkably stable (interclass coefficient = 0.90 for total IgE). Conclusions These results indicate that allergy or allergy-associated IgE may be indicative of an immune phenotype that enhances risk of SCC, possibly via immune-associate inflammatory mediators. Impact Our results indicate that controlling allergy and IgE levels may be a new avenue of skin cancer prevention in susceptible populations, and implicate immune mechanisms in skin carcinogenesis.

History of Allergy and Atopic Dermatitis in Relation to Squamous Cell and Basal Cell Carcinoma of the Skin

“…Our trend towards an increased risk of SCC associated with allergy is consistent with the two previous studies examining SCC specifically (24, 32). For example, a longitudinal cohort study from Sweden, found a positive association with SCC and asthma (SIR 1.33, 95% CI 1.19-1.48) (24).…”

“…For example, a longitudinal cohort study from Sweden, found a positive association with SCC and asthma (SIR 1.33, 95% CI 1.19-1.48) (24). A more recent nested case-control study using IgE as a biological marker for atopic allergy observed an elevated risk of SCC in relation to higher IgE levels (32). Notably, the latter study had a high proportion of men, and in our study the positive association with SCC was largely confined to men.…”

“…One cohort study examining squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) as separate outcomes (57 BCC cases, 7 SCC cases) found evidence of an increased risk of both BCC and SCC among those with a history of atopic dermatitis (31). Two further studies of SCC included a nested case-control study among skin cancer patients that reported higher pre-diagnostic IgE levels, a marker of type I hypersensitivity reactions or atopic allergy, among those who developed a new primary cutaneous SCC compared to controls who did not (32). Ji and colleagues (24) similarly found a higher risk of SCC among asthmatics compared to non-asthmatics.…”

Atopy and Specific Cancer Sites: a Review of Epidemiological Studies

“…Although not statistically significant, patients who reported a history of any allergy showed an increased risk in SCC (OR 1.2, 95 % CI 0.8-1.8) and a decreased risk in BCC (OR 0.6, 95 % CI 0.4-1.0). In a nested case-control study conducted in the USA, IgE levels were higher in cases with SCC than controls (comparing those in the highest IgE level quartile to those in the lowest) [92]. However, there was no evidence of a dose-response trend, and the results were not statistically significant (OR 1.4, 95 % CI 0.7-2.8).…”

Non-melanoma skin cancer: The hygiene hypothesis

“…They develop antibodies of the IgE-type. Patients who have multiple squamous cell carcinomas have these antibodies more often (odds ratio 3.82 [95% CI 1.05-13.88]) [15]. This suggests that patients with an impaired epidermal barrier, which is indicated by the presence of sensitisation to common allergens, are at higher risk of developing non-melanoma skin cancer.…”