← Issue №4/ week of Jul 26, 2026/Colorectal

One-carbon metabolism and chemotherapy-induced toxicities in patients with stage II-III colorectal cancer: a prospective cohort study.

From GI Signals issue №4: what this paper found, what it changes, and where it sits against the current standard of care, reviewed by Simon Mathews, MD.

Colorectal prospective cohort · n=297 · Jul 27, 2026 · Am J Clin Nutrition · IF 6.5

One-carbon metabolism and chemotherapy-induced toxicities in patients with stage II-III colorectal cancer: a prospective cohort study.

New evidencecolorectal cancerbiomarker
Clinical takeawayNo clinical action yet: associations in a prospective cohort require validation in interventional trials before modifying nutrition or supplementation.
What it foundHigher folate (HR 0.75, 95% CI 0.57-0.98) and vitamin B2 (HR 0.81, 95% CI 0.67-0.99) were associated with lower capecitabine toxicity risk specifically in patients with MTHFR C677T CT/TT genotype, while higher glycine (HR 1.87, 95% CI 1.18-2.94) increased toxicity risk. Nonlinear associations were observed for vitamin B6 and vitamin B12.
ContextSuggests potential for personalized nutrition strategies to mitigate capecitabine toxicity in patients with MTHFR C677T CT/TT genotype, but current practice does not routinely adjust OCM biomarkers pre-chemotherapy.
Measured against the standard of care· USMSTF 2017 (Rex et al., Gastroenterology) + USMSTF 2022 focused update on age (Patel et al., Gastroenterology 2022;162:285-299) / ACS 2026 (CA Cancer J Clin)

Decision at stakeoptimizing chemotherapy tolerance in stage II-III colorectal cancer patients

… Multi-Society Task Force (2017 guideline, revised by the 2022 focused update on age to start and stop): offer average-risk colorectal cancer screening to everyone aged 45-75. …

From our summary of this standard, unedited — the part the paper bears on. … marks omitted text. Our wording, not the guideline's; read the source for its own text.

Our full summary of this standard

U.S. Multi-Society Task Force (2017 guideline, revised by the 2022 focused update on age to start and stop): offer average-risk colorectal cancer screening to everyone aged 45-75. Screening at 45-49 is a weaker recommendation than at 50-75. Colonoscopy every 10 years and annual FIT are the Tier 1 cornerstones. Tier 2 alternatives are multi-target stool DNA every 3 years, CT colonography every 5 years, and flexible sigmoidoscopy every 5-10 years. Capsule colonoscopy every 5 years is Tier 3. Any abnormal non-colonoscopy test requires a diagnostic colonoscopy, and a stool test should not be offered to a patient who would decline follow-up colonoscopy. Patients who are up to date with negative prior screening, particularly a high-quality colonoscopy, may consider stopping at 75 or when life expectancy is under 10 years. Decisions at 76-85 are individualized by health and prior screening, and screening after 85 is not recommended. The American Cancer Society's May 2026 guideline agrees on the 45-75 range, no screening after 85, and colonoscopy as the preferred option. It adds the next-generation mt-sDNA test and the multitarget stool RNA test (ColoSense), both every 3 years, and it adds an FDA-approved blood-based cfDNA test (Shield) only for people who decline or do not complete visual or stool screening. ACS says a positive stool or blood test should be followed by colonoscopy, preferably within 6 months. The 2026 ASGE paper on follow-up after an abnormal stool test is an implementation review (navigation, tracking, direct-access colonoscopy), not a new screening guideline.

USMSTF 2017 (Rex et al., Gastroenterology) + USMSTF 2022 focused update on age (Patel et al., Gastroenterology 2022;162:285-299) / ACS 2026 (CA Cancer J Clin) · reviewed 2026-10-11 ↗
Zwart NRK … Kok DE · American Journal of Clinical Nutrition · IF 6.5 · PubMed ↗Permalink
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