Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma

Lesley M. Butler, Erland Arning, Renwei Wang, Teodoro Bottiglieri, Sugantha Govindarajan, Yu Tang Gao, Jian Min Yuan

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Rats fed diets deficient in choline develop hepatocellular carcinoma. Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and hepatocellular carcinoma risk have been lacking. Methods: We prospectively examined the association between prediagnostic serum concentrations of onecarbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing hepatocellular carcinoma based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate ORs and 95% confidence intervals (CI) adjusted for established risk factors for hepatocellular carcinoma. Results: Serum choline and PLP were associated with statistically significant reduced risk of hepatocellular carcinoma, whereas serum cystathionine, methionine, andSAMwere associated with increased hepatocellular carcinoma risk (all Ptrend < 0.05). The inverse associations for hepatocellular carcinoma risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16-0.78; P =0.010) and 0.44 (0.25-0.78; P = 0.005), respectively. There were no associations for hepatocellular carcinoma risk with 5-MTHF, betaine, or homocysteine. Conclusion: The inverse associations between choline and vitamin B6 and the risk of hepatocellular carcinoma development are novel and warrant further investigation. Impact: Identifying new modifiable factors for hepatocellular carcinoma prevention is warranted.

Original languageEnglish (US)
Pages (from-to)1884-1893
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

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Hepatocellular Carcinoma
Carbon
Choline
Serum
Cystathionine
Betaine
Vitamin B 6
Homocysteine
Methionine
S-Adenosylmethionine
Pyridoxal Phosphate
Case-Control Studies
China
Logistic Models
Prospective Studies
Confidence Intervals
Diet
DNA

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Butler, L. M., Arning, E., Wang, R., Bottiglieri, T., Govindarajan, S., Gao, Y. T., & Yuan, J. M. (2013). Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma. Cancer Epidemiology Biomarkers and Prevention, 22(10), 1884-1893. https://doi.org/10.1158/1055-9965.EPI-13-0497

Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma. / Butler, Lesley M.; Arning, Erland; Wang, Renwei; Bottiglieri, Teodoro; Govindarajan, Sugantha; Gao, Yu Tang; Yuan, Jian Min.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 10, 10.2013, p. 1884-1893.

Research output: Contribution to journalArticle

Butler, LM, Arning, E, Wang, R, Bottiglieri, T, Govindarajan, S, Gao, YT & Yuan, JM 2013, 'Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 10, pp. 1884-1893. https://doi.org/10.1158/1055-9965.EPI-13-0497
Butler, Lesley M. ; Arning, Erland ; Wang, Renwei ; Bottiglieri, Teodoro ; Govindarajan, Sugantha ; Gao, Yu Tang ; Yuan, Jian Min. / Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 10. pp. 1884-1893.
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abstract = "Background: Rats fed diets deficient in choline develop hepatocellular carcinoma. Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and hepatocellular carcinoma risk have been lacking. Methods: We prospectively examined the association between prediagnostic serum concentrations of onecarbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing hepatocellular carcinoma based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate ORs and 95{\%} confidence intervals (CI) adjusted for established risk factors for hepatocellular carcinoma. Results: Serum choline and PLP were associated with statistically significant reduced risk of hepatocellular carcinoma, whereas serum cystathionine, methionine, andSAMwere associated with increased hepatocellular carcinoma risk (all Ptrend < 0.05). The inverse associations for hepatocellular carcinoma risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95{\%} CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16-0.78; P =0.010) and 0.44 (0.25-0.78; P = 0.005), respectively. There were no associations for hepatocellular carcinoma risk with 5-MTHF, betaine, or homocysteine. Conclusion: The inverse associations between choline and vitamin B6 and the risk of hepatocellular carcinoma development are novel and warrant further investigation. Impact: Identifying new modifiable factors for hepatocellular carcinoma prevention is warranted.",
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T1 - Prediagnostic levels of serum one-carbon metabolites and risk of hepatocellular carcinoma

AU - Butler, Lesley M.

AU - Arning, Erland

AU - Wang, Renwei

AU - Bottiglieri, Teodoro

AU - Govindarajan, Sugantha

AU - Gao, Yu Tang

AU - Yuan, Jian Min

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N2 - Background: Rats fed diets deficient in choline develop hepatocellular carcinoma. Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and hepatocellular carcinoma risk have been lacking. Methods: We prospectively examined the association between prediagnostic serum concentrations of onecarbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing hepatocellular carcinoma based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate ORs and 95% confidence intervals (CI) adjusted for established risk factors for hepatocellular carcinoma. Results: Serum choline and PLP were associated with statistically significant reduced risk of hepatocellular carcinoma, whereas serum cystathionine, methionine, andSAMwere associated with increased hepatocellular carcinoma risk (all Ptrend < 0.05). The inverse associations for hepatocellular carcinoma risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16-0.78; P =0.010) and 0.44 (0.25-0.78; P = 0.005), respectively. There were no associations for hepatocellular carcinoma risk with 5-MTHF, betaine, or homocysteine. Conclusion: The inverse associations between choline and vitamin B6 and the risk of hepatocellular carcinoma development are novel and warrant further investigation. Impact: Identifying new modifiable factors for hepatocellular carcinoma prevention is warranted.

AB - Background: Rats fed diets deficient in choline develop hepatocellular carcinoma. Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and hepatocellular carcinoma risk have been lacking. Methods: We prospectively examined the association between prediagnostic serum concentrations of onecarbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing hepatocellular carcinoma based on a nested case-control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate ORs and 95% confidence intervals (CI) adjusted for established risk factors for hepatocellular carcinoma. Results: Serum choline and PLP were associated with statistically significant reduced risk of hepatocellular carcinoma, whereas serum cystathionine, methionine, andSAMwere associated with increased hepatocellular carcinoma risk (all Ptrend < 0.05). The inverse associations for hepatocellular carcinoma risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16-0.78; P =0.010) and 0.44 (0.25-0.78; P = 0.005), respectively. There were no associations for hepatocellular carcinoma risk with 5-MTHF, betaine, or homocysteine. Conclusion: The inverse associations between choline and vitamin B6 and the risk of hepatocellular carcinoma development are novel and warrant further investigation. Impact: Identifying new modifiable factors for hepatocellular carcinoma prevention is warranted.

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