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A prospective evaluation of serum methionine‐related metabolites in relation to pancreatic cancer risk in two prospective cohort studies
Author(s) -
Huang Joyce Y.,
Luu Hung N.,
Butler Lesley M.,
Midttun Øivind,
Ulvik Arve,
Wang Renwei,
Jin Aizhen,
Gao YuTang,
Tan Yuting,
Ueland Per M.,
Koh WoonPuay,
Yuan JianMin
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32994
Subject(s) - choline , methionine , pancreatic cancer , betaine , odds ratio , medicine , prospective cohort study , gastroenterology , homocysteine , endocrinology , cohort , cohort study , quartile , cancer , confidence interval , chemistry , biochemistry , amino acid
Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case–control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N ‐oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors and TMAO were 0.27 (0.11–0.69), 0.57 (0.31–1.05), 0.50 (0.26–0.96), 0.37 (0.19–0.73) and 2.81 (1.37–5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23–3.17), 0.50 (0.17–1.45), 0.17 (0.04–0.68), 0.33 (0.10–1.16) and 1.42 (0.50–4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota‐derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline‐pancreatic cancer risk association.