ArticleGut2016
The Thr300Ala variant in ATG16L1 is associated with improved survival in human colorectal cancer and enhanced production of type I interferon.
Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Autophagy-related genes polymorphism in hepatitis B virus-associated hepatocellular carcinoma: A systematic review.Immunity, inflammation and disease · 2024Pooled it
- Targeting cell death in Crohn's disease: from mechanisms to medicines.Cell death discovery · 2026Review
- Insufficient Expression of the Autophagic Protein ATG16L1 Results in Accelerated Carcinogenesis Related to an Aberrant B Cell Response.Cancer reports (Hoboken, N.J.) · 2026Article
- Atg16l1 and Xbp1 cooperatively protect from transcription-associated mutagenesis and small intestinal carcinogenesis.Oncogene · 2025Article
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- Autophagy related genes polymorphisms in Parkinson's Disease; A systematic review of literature.Clinical parkinsonism & related disorders · 2025Review
- Gut microbiota interplay with autophagy-EMT dynamics in colorectal cancer.Frontiers in cell and developmental biology · 2025Review
- Autophagy and its role in gastrointestinal diseases.World journal of gastroenterology · 2024Article
- Beyond self‑eating: Emerging autophagy‑independent functions for the autophagy molecules in cancer (Review).International journal of oncology · 2024Review
- Interleukin-22 Alleviates Caerulein-Induced Acute Pancreatitis by Activating AKT/mTOR Pathway.Digestive diseases and sciences · 2024Article
- Association of ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 with esophageal cancer.Molecular biology reports · 2024Article
- Article
- Metabolic reprogramming, autophagy, and ferroptosis: Novel arsenals to overcome immunotherapy resistance in gastrointestinal cancer.Cancer medicine · 2023Review
- Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer.Nature communications · 2023Article
- Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia.International journal of molecular sciences · 2023Review
- How autophagy, a potential therapeutic target, regulates intestinal inflammation.Frontiers in immunology · 2023Review
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- Article
- Alterations of autophagic and innate immune responses by the Crohn's disease-associatedWorld journal of gastroenterology · 2022Review
- Circulating microRNA sequencing revealed miRNome patterns in hematology and oncology patients aiding the prognosis of invasive aspergillosis.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveATG16L1 is an autophagy gene known to control host immune responses to viruses and bacteria. Recently, a non-synonymous single-nucleotide polymorphism in ATG16L1 (Thr300Ala), previously identified as a risk factor in Crohn's disease (CD), was associated with more favourable clinical outcomes in thyroid cancer. Mechanisms underlying this observation have not been proposed, nor is it clear whether an association between Thr300Ala and clinical outcomes will be observed in other cancers. We hypothesised that Thr300Ala influences clinical outcome in human colorectal cancer (CRC) and controls innate antiviral pathways in colon cancer cells.
designWe genotyped 460 patients with CRC and assessed for an association between ATG16L1 Thr300Ala and overall survival and clinical stage. Human CRC cell lines were targeted by homologous recombination to examine the functional consequence of loss of ATG16L1, or introduction of the Thr300Ala variant.
resultsWe found an association between longer overall survival, reduced metastasis and the ATG16L1 Ala/Ala genotype. Tumour sections from ATG16L1 Ala/Ala patients expressed elevated type I interferons (IFN-I)-inducible, MxA, suggesting that differences in cytokine production may influence disease progression. When introduced into human CRC cells by homologous recombination, the Thr300Ala variant did not affect bulk autophagy, but increased basal production of type I IFN. Introduction of Thr300Ala resulted in increased sensitivity to the dsRNA mimic poly(I:C) through a mitochondrial antiviral signalling (MAVS)-dependent pathway.
conclusionsThe CD-risk allele, Thr300Ala, in ATG16L1 is associated with improved overall survival in human CRC, generating a rationale to genotype ATG16L1 Thr300Ala in patients with CRC. We found that Thr300A alters production of MAVS-dependent type I IFN in CRC cells, providing a mechanism that may influence clinical outcomes.
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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.