IL6-174 G>C polymorphism (rs1800795) association with late effects of low dose radiation exposure in the Portuguese tinea capitis cohort

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IL6-174 G>C polymorphism (rs1800795) association with late effects of low dose radiation exposure in the Portuguese tinea capitis cohort

Tuesday, 13.12.2016

Head and neck cancers are considered late effects of low dose radiation exposure, namely in the former tinea capitis patients who were submitted to scalp irradiation, in 1950-1960, to induce epilation. In fact we have found a high prevalence of thyroid carcinoma and of basal cell carcinoma in the Portuguese tinea capitis (scalp ringworm) cohort we have been following since 2006. Recently, in the Israeli tinea capitis cohort, scalp irradiation has been shown as an independent risk factor for carotid atherosclerosis. Considering this, we randomly selected 690 from the previously observed 1375 tinea capitis patients (52.5%) to whom we were able to propose a Doppler exam, in a second evaluation directed to carotid atherosclerosis diagnosis.

Since, in addition to radiation dose, gender and younger age at exposure, the genetic background might be involved in the susceptibility to low dose radiation late effects, we decided to assess the association of the IL6-174 G>C SNP with low dose radiation effects such as thyroid carcinoma, basal cell carcinoma and carotid atherosclerosis in the Portuguese tinea capitis cohort. The -174 G>C (rs1800795) SNP in IL6 has been associated with cancer and cardiovascular disease, nevertheless this association is still controversial.

The IL6-174 G>C SNP was genotyped in 1269 individuals formerly clinical observed. This sampling group included thyroid cancer (n=36), basal cell carcinoma (n=113) and cases without thyroid or basal cell carcinoma (1120). The subgroup assessed for atherosclerosis by ultrasonography included 379 former irradiated tinea capitis patients and 222 matched controls (mainly their spouses).

Irradiation alone was not a risk factor for carotid atherosclerosis. In the irradiated group, we observed that the CC genotype was significantly associated with carotid plaque risk. We found that the IL6-174 CC genotype confers a three-fold risk for carotid atherosclerotic disease suggesting it may represent a genetic susceptibility factor in the low dose radiation context. Contrarily, we did not find a significant association of the IL6-174 C allele with thyroid carcinoma or basal cell carcinoma risk.

 

Authors and Affiliations:

Paula Boaventura, PhD1,2*; Cecília Durães, PhD1,2*; Adélia Mendes, MSc1,2; Natália Costa, PhD1,2; Inês Chora, MD3; Sara Ferreira, MD3; Emanuel Araújo, MD3; Pedro Lopes, MD3; Gilberto Rosa, MD3; Pedro Marques, MD3; Paulo Bettencourt, MD, PhD3,4; Inês Oliveira, MD3; Francisco Costa, MD3; Isabel Ramos, MD, PhD3,4; Maria José Teles, MD3,4, João Tiago Guimarães, MD, PhD3,4; Manuel Sobrinho-Simões, MD, PhD1,2,3,4; Paula Soares, PhD1,2,4

* These authors contributed equally to this work

 

1 - IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal.

2 – i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.

3 - Hospital of S. João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal.

4 - Faculty of Medicine of the University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal.

 

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.

 

Journal: Plos One

 

Link: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163474