Dataset Information

A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer.

ABSTRACT:

Background

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.

Methods

A 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.

Results

Higher 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.

Conclusions

The 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.

SUBMITTER: Huang JY

PROVIDER: S-EPMC5937773 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer.

Huang Joyce Y JY Butler Lesley M LM Midttun Øivind Ø Ulvik Arve A Wang Renwei R Jin Aizhen A Gao Yu-Tang YT Ueland Per M PM Koh Woon-Puay WP Yuan Jian-Min JM

PloS one 20180507 5

<h4>Background</h4>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.<h4>Methods</h4>A 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 ...[more]

PMID: 29734388

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Project description:Reports of neurodegenerative and psychiatric disease in former athletes have increased public concern about the acute and chronic effects of sport-related concussions (SRC). The biological factors underlying individual differences in the psychiatric sequalae of SRC and their role in potential long-term negative outcomes have not been determined. One understudied biological consequence of the known inflammatory response to concussion is the activation of a key immunoregulatory pathway, the kynurenine pathway (KP). Activation of the KP produces several neuroactive metabolites that have been associated with psychiatric and neurodegenerative diseases. We tested the hypothesis that SRC results in an elevation of serum KP metabolites with neurotoxic properties (quinolinic acid [QuinA], 3-hydroxykynurenine [3HK]) together with a reduction in the neuroprotective metabolite kynurenic acid (KynA), and that these metabolites would predict post-concussion psychological symptoms. Additionally, because brain injury is thought to prime the immune system, a secondary goal was to test the hypothesis that athletes with acute SRC and a history of prior SRC would have elevated neurotoxic relative to neuroprotective KP metabolites compared to athletes that were concussed for the first time. High school and collegiate football players (N = 1136) were enrolled at a preseason baseline visit that included clinical testing and blood specimen collection. Athletes that suffered a SRC (N = 59) completed follow-up visits within 6-hours (early-acute), at 24-48 h (late-acute) and at 8, 15, and 45 days post-injury. Uninjured contact sport (CC; N = 54) and non-contact sport athletes completed similar visits and served as controls (NCC; N = 30). SRC athletes had significantly elevated psychological symptoms, assessed using the Brief Symptom Inventory-18 (BSI), acutely following injury relative to both control groups. There was a group-by-visit interaction on the ratio of KynA to 3HK in serum, a neuroprotective index, with elevated KynA/3HK in athletes with SRC at the early-acute visit relative to later visits. Importantly, athletes with greater elevation in this neuroprotective index at the early-acute visit reported fewer depressive symptoms at the late-acute visit. Finally, SRC athletes with prior concussion had significantly lower serum KynA/QuinA at all visits compared to SRC athletes with no prior concussion, an effect driven by elevated QuinA in SRC athletes with prior concussion. These results suggest that early-acute activation of the KynA branch of the KP may protect against the development of depressive symptoms following concussion. Furthermore, they highlight the potential of serum QuinA as a biomarker for repetitive head injury and provide insight into possible mechanisms linking prior concussion with subsequent injury.

Dataset Information

A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer.

Background

Methods

Results

Conclusions

Publications

A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer.

Similar Datasets

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