Role of DNA Repair Variants and Diagnostic Radiology Exams in Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case–Control Studies - Université de Lorraine Access content directly
Journal Articles Cancer Epidemiology, Biomarkers and Prevention Year : 2021

Role of DNA Repair Variants and Diagnostic Radiology Exams in Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case–Control Studies

1 UP11 - Université Paris-Sud - Paris 11
2 IGR - Institut Gustave Roussy
3 CESP - Centre de recherche en épidémiologie et santé des populations
4 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
5 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
6 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
7 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
8 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
9 Université Paris-Saclay
10 CNRGH - Centre National de Recherche en Génomique Humaine
11 CEPH - Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris]
12 GENMED - Laboratoire d'excellence en GENomique MEDicale
13 LCE - Laboratoire de Cancérologie Expérimentale
14 JACOB - Institut de Biologie François JACOB
15 IRCM - Institut de Radiobiologie Cellulaire et Moléculaire
16 IG - Institut de Génomique d'Evry
17 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
18 Institut Jean Godinot [Reims]
19 CHU Nice - Centre Hospitalier Universitaire de Nice
20 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
21 ANTICIPE - Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers
22 Epigenetec
23 USPC - Université Sorbonne Paris Cité
24 UPD5 - Université Paris Descartes - Paris 5
25 University of Birmingham [Birmingham]

Abstract

Background: Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer. Methods: On the basis of self-declared diagnostic radiology examination records in addition to existing literature, we estimated the radiation dose delivered to the thyroid gland from diagnostic procedures during childhood and adulthood in two case-control studies conducted in France. A total of 1,071 differentiated thyroid cancer (DTC) cases and 1,188 controls from the combined studies were genotyped using a custom-made Illumina OncoArray DNA chip. We focused our analysis on variants in genes involved in DNA damage response and repair pathways, representing a total of 5,817 SNPs in 571 genes. We estimated the OR per milli-Gray (OR/mGy) of the radiation dose delivered to the thyroid gland using conditional logistic regression. We then used an unconditional logistic regression model to assess the association between DNA repair gene variants and DTC risk. We performed a meta-analysis of the two studies. Results: The OR/mGy was 1.02 (95% confidence interval, 1.00-1.03). We found significant associations between DTC and rs7164173 in CHD2 (P = 5.79 × 10-5), rs6067822 in NFATc2 (P = 9.26 × 10-5), rs1059394 and rs699517 both in ENOSF1/THYS, rs12702628 in RPA3, and an interaction between rs7068306 in MGMT and thyroid radiation doses (P = 3.40 × 10-4). Conclusions: Our results suggest a role for variants in CDH2, NFATc2, ENOSF1/THYS, RPA3, and MGMT in DTC risk. Impact: CDH2, NFATc2, ENOSF1/THYS, and RPA3 have not previously been shown to be associated with DTC risk.
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Dates and versions

hal-03378112 , version 1 (14-10-2021)

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Monia Zidane, Thérèse Truong, Fabienne Lesueur, Constance Xhaard, Emilie Cordina-Duverger, et al.. Role of DNA Repair Variants and Diagnostic Radiology Exams in Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case–Control Studies. Cancer Epidemiology, Biomarkers and Prevention, 2021, 30 (6), pp.1208-1217. ⟨10.1158/1055-9965.EPI-20-1142⟩. ⟨hal-03378112⟩
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