Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location
Abstract The location of a patient’s colorectal cancer (CRC) influences their outcome but inherited factors may also be involved. We studied 1899 patients with advanced CRC (514 had proximal colonic, 493 distal colonic and 892 rectal tumours) and carried out genome-wide association studies for survi...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-77870-0 |
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| author | Christopher Wills Katie Watts Amy Houseman Timothy S. Maughan David Fisher Nada A. Al-Tassan Richard S. Houlston Valentina Escott-Price Jeremy P. Cheadle |
| author_facet | Christopher Wills Katie Watts Amy Houseman Timothy S. Maughan David Fisher Nada A. Al-Tassan Richard S. Houlston Valentina Escott-Price Jeremy P. Cheadle |
| author_sort | Christopher Wills |
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| description | Abstract The location of a patient’s colorectal cancer (CRC) influences their outcome but inherited factors may also be involved. We studied 1899 patients with advanced CRC (514 had proximal colonic, 493 distal colonic and 892 rectal tumours) and carried out genome-wide association studies for survival. Single nucleotide polymorphisms (SNPs) suggestive of association (P < 1.0 × 10–5) were tested for replication in 5078 CRC patients from the UK Biobank. We investigated the relationship between Phosphatidylinositol 4-Kinase Type 2 Beta (PI4K2B) expression in colorectal tumours and survival in 597 patients from The Human Protein Atlas (THPA). We also analysed 3 SNPs previously associated with survival by anatomical site. We found that SNPs at 54 independent loci were suggestive of an association with survival when stratified by tumour location. rs76011559 replicated in patients with proximal tumours (COIN, COIN-B and UK Biobank combined Hazard Ratio [HR] = 1.53, 95% Confidence Intervals [CI] = 1.19–1.86, P = 7.5 × 10–7) and rs12273047 replicated in patients with rectal tumours (combined HR = 1.27, 95% CI = 1.09–1.46, P = 4.1 × 10–7). In gene analyses, PI4K2B associated with survival in patients with distal cancers (P = 2.1 × 10–6) and increased PI4K2B expression in colorectal tumours was associated with improved survival (P = 9.6 × 10–5). No previously associated SNPs were replicated. Our data identify novel loci associated with survival when stratified by tumour location. |
| format | Article |
| id | doaj-art-91b6f8efd79845ada469407bc1ff33d7 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Scientific Reports |
| spelling | doaj-art-91b6f8efd79845ada469407bc1ff33d72025-01-19T12:24:23ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-024-77870-0Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour locationChristopher Wills0Katie Watts1Amy Houseman2Timothy S. Maughan3David Fisher4Nada A. Al-Tassan5Richard S. Houlston6Valentina Escott-Price7Jeremy P. Cheadle8Division of Cancer and Genetics, School of Medicine, Cardiff UniversityDivision of Cancer and Genetics, School of Medicine, Cardiff UniversityDivision of Cancer and Genetics, School of Medicine, Cardiff UniversityCRUK/MRC Oxford Institute for Radiation Oncology, University of OxfordMRC Clinical Trials Unit, University College of LondonDepartment of Genetics, King Faisal Specialist Hospital and Research CenterDivision of Genetics and Epidemiology, The Institute of Cancer ResearchInstitute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff UniversityDivision of Cancer and Genetics, School of Medicine, Cardiff UniversityAbstract The location of a patient’s colorectal cancer (CRC) influences their outcome but inherited factors may also be involved. We studied 1899 patients with advanced CRC (514 had proximal colonic, 493 distal colonic and 892 rectal tumours) and carried out genome-wide association studies for survival. Single nucleotide polymorphisms (SNPs) suggestive of association (P < 1.0 × 10–5) were tested for replication in 5078 CRC patients from the UK Biobank. We investigated the relationship between Phosphatidylinositol 4-Kinase Type 2 Beta (PI4K2B) expression in colorectal tumours and survival in 597 patients from The Human Protein Atlas (THPA). We also analysed 3 SNPs previously associated with survival by anatomical site. We found that SNPs at 54 independent loci were suggestive of an association with survival when stratified by tumour location. rs76011559 replicated in patients with proximal tumours (COIN, COIN-B and UK Biobank combined Hazard Ratio [HR] = 1.53, 95% Confidence Intervals [CI] = 1.19–1.86, P = 7.5 × 10–7) and rs12273047 replicated in patients with rectal tumours (combined HR = 1.27, 95% CI = 1.09–1.46, P = 4.1 × 10–7). In gene analyses, PI4K2B associated with survival in patients with distal cancers (P = 2.1 × 10–6) and increased PI4K2B expression in colorectal tumours was associated with improved survival (P = 9.6 × 10–5). No previously associated SNPs were replicated. Our data identify novel loci associated with survival when stratified by tumour location.https://doi.org/10.1038/s41598-024-77870-0Colorectal cancerSurvivalTumour locationGermline variation |
| spellingShingle | Christopher Wills Katie Watts Amy Houseman Timothy S. Maughan David Fisher Nada A. Al-Tassan Richard S. Houlston Valentina Escott-Price Jeremy P. Cheadle Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location Scientific Reports Colorectal cancer Survival Tumour location Germline variation |
| title | Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location |
| title_full | Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location |
| title_fullStr | Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location |
| title_full_unstemmed | Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location |
| title_short | Relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location |
| title_sort | relationship between inherited genetic variation and survival from colorectal cancer stratified by tumour location |
| topic | Colorectal cancer Survival Tumour location Germline variation |
| url | https://doi.org/10.1038/s41598-024-77870-0 |
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