{"id":"87541ef4-7fbc-58bb-800c-4e28e5174ccb","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:vitamin-c-reduces-hypermethylation-in-tet2-carriers","predicate":"reduces","statement":"One year of oral vitamin C at 1 g/day in members of a family carrying a heterozygous truncating germline TET2 mutation reduced the proportion of hypermethylated loci and diminished gene-expression differences between carriers and non-carrier relatives.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ee91d809-d194-55cd-b7b9-3dcf6f70697e","mechanism_event_label":"One year of oral vitamin C at 1 g/day in members of a family carrying a heterozygous truncating germline TET2 mutation reduced the proportion of hypermethylated loci and diminished gene-expression differences between carriers and non-carrier relatives.","subject":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"object":{"id":"ce0e18e4-7aad-5a06-a845-dea6aea103e3","slug":"human-tet2-carrier-dna-hypermethylation","display_name":"DNA hypermethylation in TET2 germline mutation carriers","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ee91d809-d194-55cd-b7b9-3dcf6f70697e","stable_key":"a2968a2f-5b00-5212-8b8c-8a4262bcb149:vitamin-c-reduces-hypermethylation-in-tet2-carriers-event","event_type":"observed_relationship","label":"One year of oral vitamin C at 1 g/day in members of a family carrying a heterozygous truncating germline TET2 mutation reduced the proportion of hypermethylated loci and diminished gene-expression differences between carriers and non-carrier relatives.","description":"A year of vitamin C shifted the DNA marks in people born with a damaged TET2, but no cancer outcome was measured.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ce0e18e4-7aad-5a06-a845-dea6aea103e3","slug":"human-tet2-carrier-dna-hypermethylation","display_name":"DNA hypermethylation in TET2 germline mutation carriers","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"duration","value_text":"One year","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Clinical trial of one year in a single lymphoma-predisposition family; genome-wide methylation and expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Oral vitamin C 1 g/day","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"One family, no disease endpoint measured. A methylation change is a biomarker, not a demonstration that lymphoma risk fell. Registered as EudraCT 2018-000155-41.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A year of vitamin C shifted the DNA marks in people born with a damaged TET2, but no cancer outcome was measured.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[pitkanen-2023] Vitamin C boosts DNA demethylation in TET2 germline mutation carriers (2023). https://pubmed.ncbi.nlm.nih.gov/36639817/ DOI: 10.1186/s13148-022-01404-6","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Blood cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"c0d7ee7a-aeb7-5ed0-9105-d0a627540908","evidence_kind":"source_excerpt","locator":"Lines 193-201","start_line":193,"end_line":201,"excerpt":"## vitamin-c-reduces-hypermethylation-in-tet2-carriers\nOne year of oral vitamin C at 1 g/day in members of a family carrying a heterozygous truncating germline TET2 mutation reduced the proportion of hypermethylated loci and diminished gene-expression differences between carriers and non-carrier relatives.\nModel/species: Clinical trial of one year in a single lymphoma-predisposition family; genome-wide methylation and expression\nOrganism: Homo sapiens\nTissue/system: Blood cells\nExposure: Oral vitamin C 1 g/day\nDuration: One year\nLimits: One family, no disease endpoint measured. A methylation change is a biomarker, not a demonstration that lymphoma risk fell. Registered as EudraCT 2018-000155-41.\nPrimary reference: [pitkanen-2023] Vitamin C boosts DNA demethylation in TET2 germline mutation carriers (2023). https://pubmed.ncbi.nlm.nih.gov/36639817/ DOI: 10.1186/s13148-022-01404-6","model_system":"Clinical trial of one year in a single lymphoma-predisposition family; genome-wide methylation and expression","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c0b9b176-985b-55c7-b8f5-f3ca16a7ddfe","stable_key":"import-a2968a2f-5b00-5212-8b8c-8a4262bcb149","title":"TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text.","file_path":"","sha256":"22e2c8388d4f0c1813546ba6a9ccee3fa14c0c8f578bd9bd80103c1390b2536b","revision_id":"fbc29d8d-0420-562c-bfdb-1b5af42f2d08","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}