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 language | English (US) |
|---|---|
| Pages (from-to) | 1884-1893 |
| Number of pages | 10 |
| Journal | Cancer Epidemiology Biomarkers and Prevention |
| Volume | 22 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Epidemiology
- Oncology
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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 journal › Article
}
TY - JOUR
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
PY - 2013/10
Y1 - 2013/10
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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UR - http://www.scopus.com/inward/citedby.url?scp=84886425512&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-13-0497
DO - 10.1158/1055-9965.EPI-13-0497
M3 - Article
C2 - 23897582
AN - SCOPUS:84886425512
VL - 22
SP - 1884
EP - 1893
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 10
ER -