ORCID Profile
0000-0001-8139-7799
Current Organisation
Hannover Medical School
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Publisher: Elsevier BV
Date: 05-2023
Publisher: Springer Science and Business Media LLC
Date: 16-01-2020
DOI: 10.1038/S41467-019-14100-6
Abstract: Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
Publisher: Cold Spring Harbor Laboratory
Date: 04-08-2021
DOI: 10.1101/2021.08.01.21261455
Abstract: We have performed genetic correlation and Mendelian randomization analyses using publicly available genome-wide association study (GWAS) data to identify endometrial cancer risk factors. These and previously established risk factors of endometrial cancer were then included in a multi-trait Bayesian GWAS analysis to detect endometrial cancer susceptibility variants, identifying three novel loci (7q22.1, 8q24.3 and 16q12.2) two of which were replicated in an independent endometrial cancer GWAS dataset. These loci are hypothesized to affect endometrial cancer risk through altered sex-hormone levels or through effects on obesity. Consistent with this hypothesis, several genes with established roles in these pathways ( CYP11B1, CYP3A7, IRX3 and IRX5 ) were prioritized as candidate endometrial cancer risk genes by interrogation of quantitative trait loci data and chromatin capture assays in endometrial cell lines. The findings of this study identify additional opportunities for hormone treatment and further support weight loss to reduce the risk of developing endometrial cancer. This study prioritizes four genes related to testosterone and obesity as candidate endometrial cancer risk genes, as well as identifies additional opportunities for hormone treatment and further supports weight loss to reduce endometrial cancer risk.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2019
No related grants have been discovered for Dhanya Ramachandran.