IL6-174 G>C Polymorphism (rs1800795) Association with Late Effects of Low Dose Radiation Exposure in the Portuguese Tinea Capitis Cohort

PLoS One. 2016 Sep 23;11(9):e0163474. doi: 10.1371/journal.pone.0163474. eCollection 2016.

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.

Grants and funding

This work was supported with funding from Prize ACS-MERCK SERONO in Cancer Epidemiology, 2010. Funding to P.B. was obtained from FCT/MEC through National Funds and co-financed by the FEDER through the PT2020 Partnership Agreement under the project n° 007274 (UID/BIM/04293); funding to C.D. was obtained from FCT grant SFRH/BPD/62974/2009. Further funding was obtained from the project “Microenvironment, metabolism and cancer” partially supported by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN), and through the Fundo Europeu de Desenvolvimento Regional (FEDER). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. This work is funded by FEDER funds through the Operational Programme for Competitiveness Factors—COMPETE and National Funds through the FCT, under the projects "PEst-C/SAU/LA0003/2013”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.