title: Homocysteine, cysteine, and risk of incident colorectal cancer in the Women's Health Initiative observational cohort.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Davis, CA 95817, USA. jwmiller@ucdavis.edu
authors: Joshua W
authors: JW
authors: Miller
authors: Shirley A A
authors: SA
authors: Beresford
authors: Marian L
authors: ML
authors: Neuhouser
authors: Ting-Yuan David
authors: TY
authors: Cheng
authors: Xiaoling
authors: X
authors: Song
authors: Elissa C
authors: EC
authors: Brown
authors: Yingye
authors: Y
authors: Zheng
authors: Beatriz
authors: B
authors: Rodriguez
authors: Ralph
authors: R
authors: Green
authors: Cornelia M
authors: CM
authors: Ulrich
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000097:blood / Q000209:etiology*; D003545:Cysteine / Q000097:blood*; D005006:Ethnicity; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D008875:Middle Aged; D019370:Observation; D016017:Odds Ratio; D017698:Postmenopause; D012004:Rectal Neoplasms / Q000097:blood / Q000209:etiology*; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D003545:Cysteine