RT Journal Article
SR Electronic
T1 Role of DNA repair variants and diagnostic radiology exams in differentiated thyroid cancer risk: a pooled-analysis of two case-control studies
JF Cancer Epidemiology Biomarkers & Prevention
JO Cancer Epidemiol Biomarkers Prev
FD American Association for Cancer Research
SP cebp.1142.2020
DO 10.1158/1055-9965.EPI-20-1142
A1 Zidane, Monia
A1 Truong, Therese
A1 Lesueur, Fabienne
A1 Xhaard, Constance
A1 Cordina-Duverger, Emilie
A1 Boland, Anne
A1 Blanché, Hélène
A1 Ory, Catherine
A1 CHEVILLARD, Sylvie
A1 Deleuze, Jean-François
A1 Souchard, Vincent
A1 Ren, Yan
A1 Zemmache, Mohammed Zakarya
A1 Canale, Sandra
A1 Borson-Chazot, Françoise
A1 Schvartz, Claire
A1 Mariné Barjoan, Eugènia
A1 Guizard, Anne-Valerie
A1 Laurent-Puig, Pierre
A1 Mulot, Claire
A1 Guibon, Julie
A1 Karimi, Mojgan
A1 Schlumberger, Martin
A1 Adjadj, Elisabeth
A1 Rubino, Carole
A1 Guénel, Pascal
A1 Cazier, Jean-Baptiste
A1 de Vathaire, Florent
YR 2021
UL http://cebp.aacrjournals.org/content/early/2021/04/06/1055-9965.EPI-20-1142.abstract
AB Background: Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer. Methods: Based on 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 1071 differentiated thyroid cancer (DTC) cases and 1188 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 5817 single-nucleotide polymorphisms in 571 genes. We estimated the odds ratio 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% CI: 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.