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Investigation of common genetic risk factors between thyroid traits and breast cancer.
Lucotte, Elise A; Asgari, Yazdan; Sugier, Pierre-Emmanuel; Karimi, Mojgan; Domenighetti, Cloé; Lesueur, Fabienne; Boland-Augé, Anne; Ostroumova, Evgenia; de Vathaire, Florent; Zidane, Monia; Guénel, Pascal; Deleuze, Jean-François; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Liquet, Benoît; Truong, Thérèse.
Affiliation
  • Lucotte EA; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
  • Asgari Y; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
  • Sugier PE; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
  • Karimi M; Laboratoire de Mathématiques et de leurs Applications de Pau, Université de Pau et des Pays de l'Adour, UMR CNRS 5142, E2S-UPPA, 64013 Pau, France.
  • Domenighetti C; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
  • Lesueur F; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
  • Boland-Augé A; Inserm, U900, Institut Curie, PSL University, Mines ParisTech, 75006 Paris, France.
  • Ostroumova E; National Centre of Human Genomics Research, François Jacob Institute of Biology, Commissariat à l'Energie Atomique, Paris-Saclay University, 91000 Evry, France.
  • de Vathaire F; International Agency for Research on Cancer, WHO, 69007 Lyon, France.
  • Zidane M; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team of Epidemiology of radiations, 94807 Villejuif, France.
  • Guénel P; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team of Epidemiology of radiations, 94807 Villejuif, France.
  • Deleuze JF; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
  • Boutron-Ruault MC; National Centre of Human Genomics Research, François Jacob Institute of Biology, Commissariat à l'Energie Atomique, Paris-Saclay University, 91000 Evry, France.
  • Severi G; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
  • Liquet B; Paris-Saclay University, UVSQ, Gustave Roussy, Inserm, CESP, Team "Exposome and Heredity", 94807 Villejuif, France.
  • Truong T; Department of Statistics, Computer Science, Applications "G. Parenti", University of Florence, 50121 Florence, Italy.
Hum Mol Genet ; 33(1): 38-47, 2023 Dec 12.
Article in En | MEDLINE | ID: mdl-37740403
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Thyroid Gland / Breast Neoplasms Type of study: Etiology_studies / Observational_studies / Risk_factors_studies Limits: Female / Humans Language: En Journal: Hum Mol Genet Journal subject: BIOLOGIA MOLECULAR / GENETICA MEDICA Year: 2023 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Thyroid Gland / Breast Neoplasms Type of study: Etiology_studies / Observational_studies / Risk_factors_studies Limits: Female / Humans Language: En Journal: Hum Mol Genet Journal subject: BIOLOGIA MOLECULAR / GENETICA MEDICA Year: 2023 Document type: Article Affiliation country: