Abstract
Head and neck cancers, and cardiovascular disease have been described as late effects of low dose radiation (LDR) exposure, namely in tinea capitis cohorts. In addition to radiation dose, gender and younger age at exposure, the genetic background might be involved in the susceptibility to LDR late effects. The -174 G>C (rs1800795) SNP in IL6 has been associated with cancer and cardiovascular disease, nevertheless this association is still controversial. We assessed the association of the IL6-174 G>C SNP with LDR effects such as thyroid carcinoma, basal cell carcinoma and carotid atherosclerosis in the Portuguese tinea capitis cohort. The IL6-174 G>C SNP was genotyped in 1269 individuals formerly irradiated for tinea capitis. This sampling group included thyroid cancer (n = 36), basal cell carcinoma (n = 113) and cases without thyroid or basal cell carcinoma (1120). A subgroup was assessed for atherosclerosis by ultrasonography (n = 379) and included matched controls (n = 222). Genotypes were discriminated by real-time PCR using a TaqMan SNP genotyping assay. In the irradiated group, we observed that the CC genotype was significantly associated with carotid plaque risk, both in the genotypic (OR = 3.57, CI = 1.60–7.95, p-value = 0.002) and in the recessive (OR = 3.02, CI = 1.42–6.42, p-value = 0.004) models. Irradiation alone was not a risk factor for carotid atherosclerosis. We did not find a significant association of the IL6-174 C allele with thyroid carcinoma or basal cell carcinoma risk. The IL6-174 CC genotype confers a three-fold risk for carotid atherosclerotic disease suggesting it may represent a genetic susceptibility factor in the LDR context.
Highlights
Head and neck cancers are considered late effects of low dose radiation (LDR) exposure, namely in the former tinea capitis patients who were submitted to scalp irradiation to induce epilation [1]
We have found a high prevalence of basal cell carcinoma (BCC) [2] and of thyroid carcinoma (TC) [3] in the Portuguese tinea capitis cohort, in accordance with what has been previously described in similar cohorts [4,5,6]
We have evaluated the association of the Interleukin 6 (IL6)-174 G>C SNP with late effects of LDR (TC, BCC and carotid atherosclerotic disease) in a cohort of individuals irradiated in childhood for tinea capitis treatment
Summary
Head and neck cancers are considered late effects of low dose radiation (LDR) exposure, namely in the former tinea capitis patients who were submitted to scalp irradiation to induce epilation [1]. Interleukin 6 (IL6) is a cytokine with a regulatory role in cell proliferation, differentiation and the balance between pro-inflammatory and anti-inflammatory pathways [10]. It has been implicated in cardiovascular disease [11,12] and neoplastic disease [10,13]. The promoter of IL6 contains several SNPs, of which the -174 G>C is the most widely studied for its influence in various cancers [14]. Jiao and colleagues have shown the -174 G>C SNP was not associated with lung cancer as previously described [15]. Regarding TC, Schulte and colleagues found a higher C allele frequency, reaching significance only for the papillary variant [19]
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