ArticleNature2016
Substantial contribution of extrinsic risk factors to cancer development.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 300 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
300 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- A Meta-Analysis of MiRNA-497 and Prognosis of Hepatocellular Carcinoma.Canadian journal of gastroenterology & hepatology · 2024Pooled it
- Clinicopathological and Prognostic Significance of Long Non-coding RNA MIAT in Human Cancers: A Review and Meta-Analysis.Frontiers in genetics · 2021Pooled it
- Diagnostic significance and carcinogenic mechanism of pan-cancer gene POU5F1 in liver hepatocellular carcinoma.Cancer medicine · 2020Pooled it
- The level of Krüppel-like factor 8 expression predicts prognosis and metastasis in various carcinomas.Medicine · 2019Pooled it
- The Significance of Long Non-coding RNA HULC in Predicting Prognosis and Metastasis of Cancers: a Meta-Analysis.Pathology oncology research : POR · 2019Pooled it
- Dark matter matters: from noncoding RNA regulation to cancer immunity.Oncoimmunology · 2026Review
- The "Selfish Cell": The Central Role of Metabolism in Relaying Environmental Stimuli and Controlling Cellular Function.Biology · 2026Review
- Nitric Oxide in the Intestinal Stem Cell Niche: A Spatial Model of Nitrosative Stress and Clonal Evolution in Colitis-Associated Colorectal Cancer.Digestive diseases and sciences · 2026Review
- Intratumoral microbiota in the growth of CRC and lung cancer: Comprehensive insights from etiology to therapy.iScience · 2026Review
- Intensive Longitudinal Data Collection Methods in Health Research: Tutorial for Selecting Measures and Designing a Sampling Protocol.JMIR mHealth and uHealth · 2026Article
- Air pollution and hepatocellular carcinoma: Integrated network toxicology, machine learning, molecular docking and multiomics analysis.Oncology letters · 2026Article
- Tributyltin Protumorigenic Effects Targeting Prostate Cancer Cell Metabolism, Proliferation, Migration, and Invasion.Environmental toxicology · 2026Article
- Genomic landscape of ERCC alterations in breast and gynecological cancers: implications for targeted therapy and VUS reclassification.Molecular biology reports · 2026Article
- Characterization of Patients with Non-Small Cell Lung Cancer Using Machine Learning Tools: Relationship with Prognostic Biomarkers and Overall Survival-A Pilot Study.Journal of clinical medicine · 2026Article
- Stromal BMP signalling maintains stem cell genome integrity and prevents gastric cancer initiation.Cell death & disease · 2026Article
- SATB2 dysregulation generates a novel circular RNA and drives KRAS-like transcriptional reprogramming and transformation-associated phenotypes.Cell communication and signaling : CCS · 2026Article
- Article
- Multi-omics investigation of benzo[a]pyrene in gastric cancer: comprehensive network toxicology, machine learning and molecular docking approaches.Molecular diversity · 2026Article
- PDTSyn: a parameter-decomposed transformer for domain-generalized cell line-aware drug synergy prediction.Briefings in bioinformatics · 2026Article
- Current status and advances in research on the impact and mechanisms of atmospheric pollutants on gastric cancer: a narrative review.Translational cancer research · 2026Review
240 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors.
Funding
Abstract
Recent research has highlighted a strong correlation between tissue-specific cancer risk and the lifetime number of tissue-specific stem-cell divisions. Whether such correlation implies a high unavoidable intrinsic cancer risk has become a key public health debate with the dissemination of the 'bad luck' hypothesis. Here we provide evidence that intrinsic risk factors contribute only modestly (less than ~10-30% of lifetime risk) to cancer development. First, we demonstrate that the correlation between stem-cell division and cancer risk does not distinguish between the effects of intrinsic and extrinsic factors. We then show that intrinsic risk is better estimated by the lower bound risk controlling for total stem-cell divisions. Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.
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Registered trials
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.