Folic Acid: Friend or Foe in Cancer Therapy – Key Vocabulary

These vocabulary flashcards capture the essential terms and biochemical concepts discussed in the lecture on folic acid’s dual roles in cancer biology, covering metabolism, genetic factors, fortification policy, and molecular mechanisms of protection and risk.

Folate

The natural, water-soluble form of vitamin B9 found in foods such as leafy greens, citrus fruits, and meat products.

Folic Acid

The synthetic form of vitamin B9 used in supplements and food fortification; absorbed more efficiently (≈85 %) than food folate (≈50 %).

One-Carbon Metabolism

A network of biochemical reactions that transfer single-carbon units for DNA synthesis, repair, and methylation; dependent on folate and related B-vitamins.

S-Adenosylmethionine (SAM)

A universal methyl-group donor formed from methionine; influences DNA methylation and enzyme regulation such as CYP2E1.

DNA Methylation

Epigenetic modification involving addition of methyl groups to DNA (often CpG islands) that can silence or activate gene expression.

Homocysteine

A sulfur-containing amino acid; elevated blood levels are linked to cardiovascular disease and some cancers; lowered by adequate folate.

Megaloblastic Anemia

Blood disorder characterized by large, immature red cells due to folate or vitamin B12 deficiency.

Neural Tube Defect (NTD)

Birth defects of the spine or brain (e.g., spina bifida, anencephaly) prevented by maternal folic acid intake of about 400 µg/day.

Colorectal Cancer (CRC)

Cancer of the colon or rectum; folate shows both protective and potential promotional roles depending on dose and timing.

Acute Lymphoblastic Leukemia (ALL)

A childhood leukemia whose risk may be reduced by maternal folic acid supplementation.

Acute Myeloid Leukemia (AML)

A leukemia subtype; trisomy 8 is a common cytogenetic marker influenced by folate status.

Folate Receptor-Alpha (FR-α)

A high-affinity folate-binding membrane protein overexpressed in many epithelial cancers, used for targeted drug delivery.

Folate Receptor-Beta (FR-β)

Folate-binding receptor frequently expressed on myeloid cancer cells and some solid tumors.

Prostate-Specific Membrane Antigen (PSMA)

A folate hydrolase overexpressed in prostate cancer; linked to tumor grade and recurrence.

Cytochrome P450 2E1 (CYP2E1)

An enzyme that metabolizes ethanol to acetaldehyde; its expression can be down-regulated by higher folate/SAM levels.

Aldehyde Dehydrogenase 1 (ALDH1)

A detoxifying enzyme for acetaldehyde; folate can enhance ALDH1 gene expression, potentially reducing oral cancer risk.

5,10-Methylenetetrahydrofolate Reductase (MTHFR)

Key folate-cycle enzyme; C677T and A1298C polymorphisms alter folate metabolism and modify cancer risk.

Serine Hydroxymethyltransferase (SHMT)

Enzyme providing one-carbon units for folate cycle; genetic variants interact with folate status in lung-cancer risk.

SLC19A1 (RFC-1)

Reduced folate carrier gene; c.80G>A polymorphism influences folate transport and lung-cancer susceptibility.

E-Cadherin

Cell-adhesion glycoprotein acting as tumor suppressor; high folic acid (100 ng/mL) can down-regulate its expression in colon cancer cells.

Oxidative Stress

Imbalance between free-radical production and antioxidant defenses; folic acid can act as free-radical scavenger.

Unmetabolized Folic Acid

Circulating folic acid not converted to reduced forms when intake exceeds ≈200 µg; potential links to cognitive issues and cancer.

Folic Acid Fortification

Mandatory addition of folic acid to staple foods (e.g., flour) to prevent NTDs; implemented in >80 countries since 1998.

Upper Tolerable Intake Level (UL)

Maximum daily folic acid intake unlikely to cause adverse effects; excessive supplementation may surpass the UL.

‘Acceleration Phenomenon’

Historical observation where high-dose folic acid accelerated leukemic cell proliferation (Sidney Farber, 1940s).

Mandatory vs. Voluntary Fortification

Approaches where governments require or merely allow folic-acid addition to foods; Europe mainly voluntary, Americas mandatory.

5-Fluorouracil

Antimetabolite chemotherapy that targets thymidylate synthase; efficacy relates to folate levels in cancer cells.

Trisomy 8

Chromosomal abnormality often seen in AML; incidence may rise with folate deficiency–induced chromosomal instability.

One-Carbon Nutrient Synergy

Interactive protective effect against certain cancers when folate is combined with other B-vitamins related to methylation (e.g., B6, B12).

Folic-Acid–Cancer Dichotomy

Concept that folate can prevent cancer initiation when adequate but potentially promote growth of existing lesions at high doses.