Homocysteine, cysteine, and risk of incident colorectal cancer in the Women’s Health Initiative observational cohort
- 1 April 2013
- journal article
- Published by Elsevier BV in The American Journal of Clinical Nutrition
- Vol. 97 (4), 827-834
- https://doi.org/10.3945/ajcn.112.049932
Abstract
Background: Inflammation underlies the etiology of colorectal cancer (CRC). Hyperhomocysteinemia is associated with inflammation and may be a risk marker for CRC. Cysteine is a metabolic product of homocysteine and a precursor of the antioxidant glutathione. It is unknown whether cysteine is associated with CRC. Objective: The objective was to assess the associations between homocysteine and cysteine and CRC incidence in postmenopausal women. Design: Associations between homocysteine and cysteine and incident CRC in the Women’s Health Initiative observational cohort were assessed by using a nested case-control design. Cases and controls (n = 988/group) were matched for age (mean ± SD age: 67 ± 7 y), ethnicity (85.2% white, 8.9% black, 2.2% Hispanic/Latina, and 3.6% other), hysterectomy status, and date of blood draw. Homocysteine and cysteine were measured by HPLC with postcolumn fluorimetric detection. Results: Multivariate-adjusted ORs (95% CIs) for CRC were 1.46 (1.05, 2.04) for the highest quartile of homocysteine (>9.85 μmol/L) compared with the lowest quartile (≤6.74 μmol/L) (P = 0.02) and 0.57 (0.40, 0.82) for the highest quartile of cysteine (>309 μmol/L) compared with the lowest quartile (≤260 μmol/L) (P = 0.01). The association with homocysteine was significant for proximal colon tumors (P = 0.008) but not for distal or rectal tumors, whereas the association with cysteine was significant for rectal tumors (P = 0.02), borderline for proximal tumors (P = 0.06), and not significant for distal tumors. The associations with both homocysteine and cysteine were significant for localized tumors (P ≤ 0.01) but not for metastases. Conclusion: High plasma homocysteine is associated with increased risk of CRC, whereas high cysteine is associated with decreased risk. This trial was registered at clinicaltrials.gov as NCT 00000611.This publication has 30 references indexed in Scilit:
- Concentration of folate in colorectal tissue biopsies predicts prevalence of adenomatous polypsGut, 2010
- Baseline Plasma Total Homocysteine and Adenoma Recurrence: Results from a Double Blind Randomized Clinical Trial of Aspirin and Folate SupplementationCancer Epidemiology, Biomarkers & Prevention, 2010
- Serum Adiponectin, Leptin, C-Peptide, Homocysteine, and Colorectal Adenoma Recurrence in the Polyp Prevention TrialCancer Epidemiology, Biomarkers & Prevention, 2010
- Convergence of Hormones, Inflammation, and Energy-Related Factors: A Novel Pathway of Cancer EtiologyCancer Prevention Research, 2009
- Plasma Levels of B Vitamins and Colorectal Cancer Risk: The Multiethnic Cohort StudyCancer Epidemiology, Biomarkers & Prevention, 2009
- Prospective Study of Plasma Vitamin B6 and Risk of Colorectal Cancer in MenCancer Epidemiology, Biomarkers & Prevention, 2009
- One-Carbon Metabolism Biomarkers and Risk of Colon and Rectal CancersCancer Epidemiology, Biomarkers & Prevention, 2008
- Low folate levels may protect against colorectal cancerGut, 2006
- Folate fortification, plasma folate, homocysteine and colorectal adenoma recurrenceInternational Journal of Cancer, 2006
- Modulation of tumor necrosis factor-α-mediated cytotoxicity by changes of the cellular methylation state: mechanism and in vivo relevanceInternational Immunology, 1999