ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2016
A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts.Nature communications · 2021Pooled it
- Genetic variants of genes in the NER pathway associated with risk of breast cancer: A large-scale analysis of 14 published GWAS datasets in the DRIVE study.International journal of cancer · 2019Pooled it
- Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.Genes & diseases · 2027Review
- Is Male Infertility an Early Warning of More Serious Diseases?Endocrinology · 2026Review
- From Genes to Lives: Integrating the Complexities of Primary Ovarian Insufficiency.International journal of molecular sciences · 2026Review
- Targeting DNA Damage Repair to Enhance Antitumor Immunity in Radiotherapy: Mechanisms and Opportunities.International journal of molecular sciences · 2025Review
- Identification of DNA damage repair-related genes in sepsis using bioinformatics and machine learning: An observational study.Medicine · 2025Observational
- Nonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology.Trends in cancer · 2025Review
- HMCN1 as a conserved biomarker of epithelial-mesenchymal transition: a cross-cancer analysis.Frontiers in oncology · 2025Article
- Mutation profile and molecular heterogeneity in mismatch repair deficient endometrial carcinoma.Frontiers in oncology · 2025Article
- Nucleus-targeted Silencer nanoplatform regulating ZEB1-AS1 in head and neck squamous cell carcinoma therapy.Discover nano · 2024Article
- A maternal germline mutator phenotype in a family affected by heritable colorectal cancer.Genetics · 2024Article
- A maternal germline mutator phenotype in a family affected by heritable colorectal cancer.medRxiv : the preprint server for health sciences · 2024Article
- Article
- Navigating through novelties concerning mCRC treatment-the role of immunotherapy, chemotherapy, and targeted therapy in mCRC.Frontiers in surgery · 2024Review
- A Bayesian framework for pathway-guided identification of cancer subgroups by integrating multiple types of genomic data.Statistics in medicine · 2023Article
- Uncover DNA damage and repair-related gene signature and risk score model for glioma.Annals of medicine · 2023Article
- Differences in DNA damage repair gene mutations between left- and right-sided colorectal cancer.Cancer medicine · 2023Article
- A novel DNA damage repair gene-related prognostic model for evaluating the prognosis and tumor microenvironment infiltration of esophageal squamous cell carcinoma.BMC medical genomics · 2023Article
- Rare variants confer shared susceptibility to gastrointestinal tract cancer risk.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundDNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility.
methodsWe conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling.
resultsWe identified three susceptibility DNA repair genes, RAD51B (P < 5.09 × 10(-6)), MSH5 (P < 5.09 × 10(-6)), and BRCA2 (P = 5.70 × 10(-6)). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways.
conclusionsOnly three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. IMPACT: Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria.
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