Abstract
BackgroundSerum pyridoxal 5’-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking.MethodsA nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer.ResultsHigher serum concentrations of 3-hydroxyanthranilic acid (HAA) and the HAA:3-hydroxykynurenine (HK) ratio (a measure for in vivo functional status of PLP) were significantly associated with reduced risk of pancreatic cancer. Compared with the lowest tertile, odds ratios (95% confidence intervals) of pancreatic cancer for the highest tertile was 0.62 (0.39, 1.01) for HAA, and 0.59 (0.35–0.98) for the HAA:HK ratio, after adjustment for potential confounders and serum PLP (both Ps for trend<0.05). The kynurenine:tryptophan ratio or neopterin was not significantly associated with pancreatic cancer risk.ConclusionsThe inverse association between HAA or the HAA:HK ratio and risk of pancreatic cancer supports the notion that functional status of PLP may be a more important measure than circulating PLP alone for the development of pancreatic cancer.
Highlights
Pancreatic cancer is among the deadliest malignancies in the world [1]
The inverse association between hydroxyanthranilic acid (HAA) or the HAA:HK ratio and risk of pancreatic cancer supports the notion that functional status of Pyridoxal 5’-phosphate (PLP) may be a more important measure than circulating PLP alone for the development of pancreatic cancer
Our group previously reported that dietary intake of vitamin B6 and/or PLP level in serum samples collected prior to cancer diagnosis were inversely associated with risk of pancreatic cancer [9, 10]
Summary
Pancreatic cancer is among the deadliest malignancies in the world [1]. Few primary prevention strategies are available for pancreatic cancer; only one-third of pancreatic cancer burden is attributed to smoking and obesity, the two established modifiable risk factors of pancreatic cancer [2, 3]. Studies are needed to identify novel risk or protective factors for pancreatic cancer in order to develop strategies for monitoring high-risk populations and reducing risk through primary prevention intervention. Much attention has been paid to the metabolomics biomarkers in relation to the risk assessment or clinical diagnosis of pancreatic cancer [4,5,6,7]. Our group previously reported that dietary intake of vitamin B6 and/or PLP level in serum samples collected prior to cancer diagnosis were inversely associated with risk of pancreatic cancer [9, 10]. Serum pyridoxal 5’-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking
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