Year: 2023
Type: article
Study design: Observational Study
Abstract: Breast cancer (BC) risk is suspected to be linked to thyroid disorders, however observational studies exploring the association between BC and thyroid disorders gave conflicting results. We proposed an alternative approach by investigating the shared genetic risk factors between BC and several thyroid traits. We report a positive genetic correlation between BC and thyroxine (FT4) levels (corr = 0.13, p-value = 2.0 × 10-4) and a negative genetic correlation between BC and thyroid-stimulating hormone (TSH) levels (corr = -0.09, p-value = 0.03). These associations are more striking when restricting the analysis to estrogen receptor-positive BC. Moreover, the polygenic risk scores (PRS) for FT4 and hyperthyroidism are positively associated to BC risk (OR = 1.07, 95%CI: 1.00-1.13, p-value = 2.8 × 10-2 and OR = 1.04, 95%CI: 1.00-1.08, p-value = 3.8 × 10-2, respectively), while the PRS for TSH is inversely associated to BC risk (OR = 0.93, 95%CI: 0.89-0.97, p-value = 2.0 × 10-3). Using the PLACO method, we detected 49 loci associated to both BC and thyroid traits (p-value < 5 × 10-8), in the vicinity of 130 genes. An additional colocalization and gene-set enrichment analyses showed a convincing causal role for a known pleiotropic locus at 2q35 and revealed an additional one at 8q22.1 associated to both BC and thyroid cancer. We also found two new pleiotropic loci at 14q32.33 and 17q21.31 that were associated to both TSH levels and BC risk. Enrichment analyses and evidence of regulatory signals also highlighted brain tissues and immune system as candidates for obtaining associations between BC and TSH levels. Overall, our study sheds light on the complex interplay between BC and thyroid traits and provides evidence of shared genetic risk between those conditions.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddad159
Authors: Elise A Lucotte, Yazdan Asgari, Pierre-Emmanuel Sugier, Mojgan Karimi, Cloé Domenighetti, Fabienne Lesueur, Anne Boland-Augé, Evgenia Ostroumova, Florent de Vathaire, Monia Zidane, Pascal Guénel, Jean-François Deleuze, Marie-Christine Boutron-Ruault, Gianluca Severi, Benoît Liquet, Thérèse Truong
Institutions: Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Centre de recherche en Epidémiologie et Santé des Populations, Centre National de la Recherche Scientifique, Université de Pau et des Pays de l'Adour, Laboratoire de Mathématiques et de leurs Applications, Université Paris Sciences et Lettres, École Nationale Supérieure des Mines de Paris, Institut Curie, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Centre National de Recherche en Génomique Humaine, Institut de biologie François Jacob, Centre international de recherche sur le cancer, University of Florence, Macquarie University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,181
Funders: World Health Organization, Genome Canada, Government of Canada, Cancer Research UK, European Commission, Institut National de la Santé et de la Recherche Médicale, Institut National Du Cancer, National Institutes of Health, Horizon 2020 Framework Programme, Canadian Institutes of Health Research, National Cancer Institute, Division of Arctic Sciences
Awards: G108862473, G1161123863, G1203839305, G1237735023, G1278116854, G1378522051, G1389895161, G183579924, G197189410, G2003194899, G2004299919, G236237718, G2373099447, G2395980551, Breast CAncer STratification: understanding the determinants of risk and prognosis of molecular subtypes, G2439210756, G2453522775, Discovery, Biology and Risk of Inherited Variants in Breast Cancer, G2620578876, G2708997719, G271288088, G2718683818, G2806648933, G2969180462, G3385934250, G3488400535, G3499900790, G3632654466, G3714974232, Breast Cancer Risk after Diagnostic Gene Sequencing (BRIDGES), G3807225764, G3830541857, G4168635842, G4197410787, G4321622477, G444765703, G4715308887, G4750055453, G4809228870, G4831231924, G4937468798, G494830712, G5045046497, G5050703329, G5052768465, G5181373253, G5338223732, G5566577447, G5568856568, G6229591247, G6402876381, G6744381054, G6990806275, G711535872, G7356174861, G7375233134, G7469845195, G7501896692, G7510707455, G751661945, G7625083360, G7663583697, G7684595986, G790382466, G7973277461, G8181826844, G829717837, G8392881711, Collaborative Oncological Gene-environment Study, G8441055101, G8668082143, G880611044, G8858395165, G8959936493, G8976871661, G9000025899, G997875987
OpenAlex ID: W4386979753