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

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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

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Homocysteine
Women's Health
Cysteine
Colorectal Neoplasms
Rectal Neoplasms
Hispanic Americans
Neoplasms
Inflammation
Hyperhomocysteinemia
Hysterectomy
Glutathione
Colon
Research Design
Antioxidants
High Pressure Liquid Chromatography
Neoplasm Metastasis
Incidence

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Miller, J. W., Shirley, A. A. B., Neuhouser, M. L., Cheng, T. Y. D., Song, X., Brown, E. C., ... 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

Homocysteine, cysteine, and risk of incident colorectal cancer in the Women's Health Initiative observational cohort. / Miller, Joshua W.; Shirley, A. A Beresford; Neuhouser, Marian L.; Cheng, Ting Yuan David; Song, Xiaoling; Brown, Elissa C.; Zheng, Yingye; Rodriguez, Beatriz; Green, Ralph; Ulrich, Cornelia M.

In: American Journal of Clinical Nutrition, Vol. 97, No. 4, 01.04.2013, p. 827-834.

Research output: Contribution to journalArticle

Miller, JW, Shirley, AAB, Neuhouser, ML, Cheng, TYD, Song, X, Brown, EC, Zheng, Y, Rodriguez, B, Green, R & Ulrich, CM 2013, 'Homocysteine, cysteine, and risk of incident colorectal cancer in the Women's Health Initiative observational cohort', American Journal of Clinical Nutrition, vol. 97, no. 4, pp. 827-834. https://doi.org/10.3945/ajcn.112.049932
Miller, Joshua W. ; Shirley, A. A Beresford ; Neuhouser, Marian L. ; Cheng, Ting Yuan David ; Song, Xiaoling ; Brown, Elissa C. ; Zheng, Yingye ; Rodriguez, Beatriz ; Green, Ralph ; Ulrich, Cornelia M. / Homocysteine, cysteine, and risk of incident colorectal cancer in the Women's Health Initiative observational cohort. In: American Journal of Clinical Nutrition. 2013 ; Vol. 97, No. 4. pp. 827-834.
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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.",
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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

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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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