Common shared genetic variation behind decreased risk of breast cancer in celiac diseaseShow others and affiliations
2017 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 5942
Article in journal (Refereed) Published
Abstract [en]
There is epidemiologic evidence showing that women with celiac disease have reduced risk of later developing breast cancer, however, the etiology of this association is unclear. Here, we assess the extent of genetic overlap between the two diseases. Through analyses of summary statistics on densely genotyped immunogenic regions, we show a significant genetic correlation (r = -0.17, s.e. 0.05, P < 0.001) and overlap (Ppermuted < 0.001) between celiac disease and breast cancer. Using individuallevel genotype data from a Swedish cohort, we find higher genetic susceptibility to celiac disease summarized by polygenic risk scores to be associated with lower breast cancer risk (ORper-SD, 0.94, 95% CI 0.91 to 0.98). Common single nucleotide polymorphisms between the two diseases, with low P-values (P-CD < 1.00E-05, P-BC <= 0.05), mapped onto genes enriched for immunoregulatory and apoptotic processes. Our results suggest that the link between breast cancer and celiac disease is due to a shared polygenic variation of immune related regions, uncovering pathways which might be important for their development.
Place, publisher, year, edition, pages
Nature Publishing Group, 2017. Vol. 7, article id 5942
National Category
Medical Genetics and Genomics Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-59308DOI: 10.1038/s41598-017-06287-9ISI: 000405895900007PubMedID: 28725034Scopus ID: 2-s2.0-85025116632OAI: oai:DiVA.org:oru-59308DiVA, id: diva2:1136193
Funder
Swedish Research Council, 2014-2271Swedish Cancer Society, CAN 2016/684
Note
Funding Agencies:
Cancer Society in Stockholm 141092
Ollie and Elof Ericsson Foundation
Åke Wiberg Foundation M16-0019
Singapore National Research Foundation Fellowship
Cancer Research UK C1287/A16563 C1287/A10118 C1287/A 10710 C12292/A11174 C1281/A12014 C5047/A8384 C5047/A15007 C5047/A10692 C8197/A16565
European Community's Seventh Framework Programme 223175 HEALTH-F2-2009-223175 223175 (HEALTH-F2-2009-223175)
National Institutes of Health CA128978
Post-Cancer GWAS initiative 1U19 CA148537 1U19 CA148065 1U19 CA148112
Department of Defence W81XWH-10-1-0341
Canadian Institutes of Health Research (CIHR)
Komen Foundation for the Cure
Breast Cancer Research Foundation
Ovarian Cancer Research Fund
2017-08-252017-08-252025-02-10Bibliographically approved