Analysis of the pleiotropy between breast cancer and thyroid cancer

Abstract

Thyroid and breast cancers share a lot of similarities in their biology: both are more frequent in women and are influenced by hormonal and reproductive factors. Moreover, individuals diagnosed with breast cancer are more likely to develop thyroid cancer as a secondary malignancy than patient diagnosed with other cancer types, and vice-versa (Nielsen et al., 2016). Genetic factors contributing to the incidence of breast cancer have been extensively studied, and 313 risk variants were identified (Mavaddat et al., 2019). On the other hand, GWAS studies on thyroid cancer have been scarce due to the lesser incidence of this disease as well as the lack of data, but it is known that thyroid cancer is the only cancer for which genetic factors contribute more than environmental factors. For thyroid cancer 10 loci were identified (Gudmundsson et al., 2017), and one of them (2q35) was previously reported to increase risk of breast cancer (Stacey et al., 2007). To date, no study has been conducted to identify common genetic factors between breast and thyroid cancer. We have access to GWAS results on thyroid cancer (EPITHYR consortium), which was coordinated by our team, and to the summary statistics of the most recent GWAS conducted by the Breast Cancer Association Consortium (BCAC, Michailidou et al., 2017). In this ongoing study, we aim at studying pleiotropy between both cancers at different scales. First, we will estimate the genome-wide genetic correlation using the LDscore and SumHer methods. Second, we will analyze the association of the polygenic risk scores of breast cancer in association to thyroid cancer risk and vice-versa. Third, we will identify the pleiotropic SNPs affecting both cancers. These analyses are still ongoing and the results will be presented. Evidence of carcinogenic pleiotropy will improve our understanding of the diseases etiology and will provide insights on the underlying common biology between both cancers. This work is supported by “La Ligue contre le Cancer” through the CCGIP (Cross Cancer Genomic Investigation of Pathway analysis and GxE interactions) project.