SynthesisHuman molecular genetics2023
Cross-cancer pleiotropic analysis identifies three novel genetic risk loci for colorectal cancer.
Synthesis in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Large-scale pleiotropic analysis across cancers reveals shared genetic mechanisms and identifies novel functional genes.Briefings in bioinformatics · 2026Article
- Unsupervised characterization of 100,272 EHR patients identifies high-risk groups and comorbidities linked to premature aging.NPJ digital medicine · 2026Article
- Multiple polygenic score approach in colorectal cancer risk prediction.Scientific reports · 2025Article
- Exploring new mechanisms in cancer molecular pathways and pathogenic cell transformation: PIP4K2A as a prognostic marker and therapeutic target in cutaneous malignant melanoma.Discover oncology · 2024Article
- The relationship between innate/adaptive immunity and gastrointestinal cancer : a multi-omics Mendelian randomization study.BMC gastroenterology · 2024Article
- Immunotherapy for colorectal cancer: insight from inherited genetics.Trends in cancer · 2024Review
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundTo understand the shared genetic basis between colorectal cancer (CRC) and other cancers and identify potential pleiotropic loci for compensating the missing genetic heritability of CRC.
methodsWe conducted a systematic genome-wide pleiotropy scan to appraise associations between cancer-related genetic variants and CRC risk among European populations. Single nucleotide polymorphism (SNP)-set analysis was performed using data from the UK Biobank and the Study of Colorectal Cancer in Scotland (10 039 CRC cases and 30 277 controls) to evaluate the overlapped genetic regions for susceptibility of CRC and other cancers. The variant-level pleiotropic associations between CRC and other cancers were examined by CRC genome-wide association study meta-analysis and the pleiotropic analysis under composite null hypothesis (PLACO) pleiotropy test. Gene-based, co-expression and pathway enrichment analyses were performed to explore potential shared biological pathways. The interaction between novel genetic variants and common environmental factors was further examined for their effects on CRC.
resultsGenome-wide pleiotropic analysis identified three novel SNPs (rs2230469, rs9277378 and rs143190905) and three mapped genes (PIP4K2A, HLA-DPB1 and RTEL1) to be associated with CRC. These genetic variants were significant expressions quantitative trait loci in colon tissue, influencing the expression of their mapped genes. Significant interactions of PIP4K2A and HLA-DPB1 with environmental factors, including smoking and alcohol drinking, were observed. All mapped genes and their co-expressed genes were significantly enriched in pathways involved in carcinogenesis.
conclusionOur findings provide an important insight into the shared genetic basis between CRC and other cancers. We revealed several novel CRC susceptibility loci to help understand the genetic architecture of CRC.
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