The first study establishing exposure to ionizing radiations (IRs) as a risk factor for differentiated thyroid cancer (DTC) was published 70 years ago. Given that radiation exposure causes direct DNA damage, genetic alterations in the different DNA repair mechanisms are assumed to play an important role in long-term IR-induced DNA damage prevention. Individual variations in DNA repair capacity may cause different reactions to damage made by IR exposure. The aim of this review is to recapitulate current knowledge about constitutional genetic polymorphisms found to be significantly associated with DTC occurring after IR exposure. Studies were screened online using electronic databases – only fully available articles, and studies performed among irradiated population or taking radiation exposure as adjustment factors and showing significant results are included. Nine articles were identified. Ten variants in/near to genes in six biological pathways, namely thyroid activity regulations, generic transcription, RET signaling, ATM signaling and DNA repair pathways were found to be associated with radiation-related DTC in these studies. Only seven variants were found to be in interaction with IR exposure in DTC risk. Most of these variants are also associated to sporadic DTC and are not specific to IR-related DTC. In the published studies, no data on children treated with radiotherapy is described. In conclusion, more studies carried out on larger cohorts or on case–control studies with well-documented individual radiation dose estimations are needed to get a comprehensive picture of genetic susceptibility factors involved in radiation-related DTC.
Monia Zidane, Jean-Baptiste Cazier, Sylvie Chevillard, Catherine Ory, Martin Schlumberger, Corinne Dupuy, Jean-François Deleuze, Anne Boland, Nadia Haddy, Fabienne Lesueur and Florent de Vathaire
Rafael Ríos, Carmen Belén Lupiañez, Daniele Campa, Alessandro Martino, Joaquin Martínez-López, Manuel Martínez-Bueno, Judit Varkonyi, Ramón García-Sanz, Krzysztof Jamroziak, Charles Dumontet, Andrés Jerez Cayuela, Marzena Wętek, Stephano Landi, Anna Maria Rossi, Fabienne Lesueur, Rui Manuel Reis, Victor Moreno, Herlander Marques, Artur Jurczyszyn, Vibeke Andersen, Ulla Vogel, Gabriele Buda, Enrico Orciuolo, Svend E H Jacobsen, Mario Petrini, Annette J Vangsted, Federica Gemignani, Federico Canzian, Manuel Jurado and Juan Sainz
Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case–control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the KCNQ1 rs2237892T allele or the CDKN2A-2B rs2383208G/G, IGF1 rs35767T/T and MADD rs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32–2.13) whereas those carrying the KCNJ11 rs5215C, KCNJ11 rs5219T and THADA rs7578597C alleles or the FTO rs8050136A/A and LTA rs1041981C/C genotypes showed a significantly decreased risk of developing the disease (OR=0.76–0.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10− 06). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30 rs2641348 and NOTCH2 rs10923931 variants (P interaction=0.001 and 0.0004, respectively). Men carrying the ADAM30 rs2641348C and NOTCH2 rs10923931T alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (ORM=0.71 and ORM=0.66 vs ORW=1.22 and ORW=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.