ArticleBMC medical genomics2023
Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence.
Article in BMC medical genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Combining genome-wide polygenic scores with registry data for colorectal cancer risk-based screening.British journal of cancer · 2026Article
- Polygenic risk scores in cancer.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- An introduction to polygenic scores - methodological basics and recent advances.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Transitioning from the Prospective Lynch Syndrome Database (PLSD) to the International Lynch Syndrome Database (ILSD).Familial cancer · 2026Article
- Polygenic scores as modifiers in Mendelian diseases.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Effect of a polygenic risk score in patients with late-onset, early-onset, familial, or hereditary colorectal cancer.JNCI cancer spectrum · 2026Article
- Molecular Basis of Adenomatous Gastrointestinal Polyposis Syndromes: Role of Pathogenic and Benign Variants in Disease Onset.Biomedicines · 2026Article
- Interactions with polygenic background impact quantitative traits in the UK Biobank.medRxiv : the preprint server for health sciences · 2025Article
- Modifiable lifestyle factors and genetic risk of obesity in Indians.Scientific reports · 2025Article
- Penetrance of Parkinson's disease in GBA1 carriers depends on variant severity and polygenic background.NPJ Parkinson's disease · 2025Article
- High familial risks in some rare cancers may pinpoint to hidden germline genetics: focus on esophageal, stomach, small intestinal, testis, thyroid and bone cancers.Hereditary cancer in clinical practice · 2025Review
- Whole Exome-Wide Association Identifies Rare Variants inCancers · 2024Article
- Rare germline chromosome 1 duplication identified in young male with colon cancer: a case report investigating causality.Journal of gastrointestinal oncology · 2024Article
- Estimating cancer risk in carriers of Lynch syndrome variants in UK Biobank.Journal of medical genetics · 2024Article
- Polygenic Risk Score (PRS) Combined with NGS Panel Testing Increases Accuracy in Hereditary Breast Cancer Risk Estimation.Diagnostics (Basel, Switzerland) · 2024Article
- Gastrointestinal Cancer Precursor Conditions and Their Detection.Hematology/oncology clinics of North America · 2024Review
- Colorectal Cancer Risk between Mendelian and Non-Mendelian Inheritance.Clinics in colon and rectal surgery · 2024Review
- Genome-wide polygenic risk scores for colorectal cancer have implications for risk-based screening.British journal of cancer · 2024Article
- Influence of family history on penetrance of hereditary cancers in a population setting.EClinicalMedicine · 2023Article
- Assessing the performance of European-derived cardiometabolic polygenic risk scores in South-Asians and their interplay with family history.BMC medical genomics · 2023Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsSummarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification.
methodsTo assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (< 20%), intermediate (20-80%), or high PRS (> 80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios and to compute the lifetime incidence, respectively.
resultsDepending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6 and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve in risk prediction (0.704).
conclusionThe findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.