TY - JOUR
T1 - Homocysteine, cysteine, and risk of incident colorectal cancer in the Women's Health Initiative observational cohort
AU - Miller, Joshua W.
AU - Shirley, A. A Beresford
AU - Neuhouser, Marian L.
AU - Cheng, Ting Yuan David
AU - Song, Xiaoling
AU - Brown, Elissa C.
AU - Zheng, Yingye
AU - Rodriguez, Beatriz
AU - Green, Ralph
AU - Ulrich, Cornelia M.
PY - 2013/4/1
Y1 - 2013/4/1
N2 - 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.
AB - 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.
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U2 - 10.3945/ajcn.112.049932
DO - 10.3945/ajcn.112.049932
M3 - Article
C2 - 23426034
AN - SCOPUS:84875827580
VL - 97
SP - 827
EP - 834
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
SN - 0002-9165
IS - 4
ER -