Homocysteine, cysteine, and risk of incident colorectal cancer in the Women's Health Initiative observational cohort

Joshua W. Miller, A. A.Beresford Shirley, Marian L. Neuhouser, Ting Yuan David Cheng, Xiaoling Song, Elissa C. Brown, Yingye Zheng, Beatriz Rodriguez, Ralph Green, Cornelia M. Ulrich

Research output: Contribution to journalArticle

50 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)827-834
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Volume97
Issue number4
DOIs
StatePublished - Apr 1 2013

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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    Miller, J. W., Shirley, A. A. B., Neuhouser, M. L., Cheng, T. Y. D., Song, X., Brown, E. C., Zheng, Y., Rodriguez, B., Green, R., & Ulrich, C. M. (2013). Homocysteine, cysteine, and risk of incident colorectal cancer in the Women's Health Initiative observational cohort. American Journal of Clinical Nutrition, 97(4), 827-834. https://doi.org/10.3945/ajcn.112.049932