One carbon metabolism and pancreatic cancer

  • Topic: Pancreatic Cancer
  • Institution: Imperial College London
  • Country: United Kingdom
  • Status: Completed

Scientific abstract

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Background & Aim

In previous research, folate intake has shown an inverse association with pancreatic cancer; however, results from plasma measurements were inconsistent. The aim of this study was to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5’-phosphate, riboflavin, and flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods

We conducted a nested case-control study in the EPIC cohort, which had an average of 9.6 years of follow-up at the time (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/-1y), date (+/-1y) and time (+/-3h) at blood collection, and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status.

Results

We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate ≤5, 5-10, 10-15 (reference), 15-20, and >20 nmol/L were 1.58 (95% CI=0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR=1.17 95% CI=1.00-1.38) but not in women (OR=0.91, 95% CI=0.78-1.07; p for heterogeneity<0.01).

Conclusions

Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex-dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.

Plain language abstract

Hypothesis

The hypothesis is that folate deficiency increases the risk of pancreatic cancer. This knowledge could be used for primary dietary prevention.

Background

Folate intake has shown an inverse association with pancreatic cancer in previous studies; nevertheless, results from plasma measurements were inconsistent.

Methods

We conducted a nested study in the EPIC cohort, which had an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases and their matched healthy controls. Multivariate analysis was used to calculate the relative risks of folate-related disease and statistical confidence intervals, adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status.

Key findings

We observed a U-shaped association between plasma folate and pancreatic cancer risk. The risk of pancreatic cancer for plasma folate levels ≤5, 5-10, 10-15 (reference), 15-20, and >20 nmol/L increased by 58% (<5), 39% (5-10) and 34% (>20), but decreased by 79% in the 15-20 category, using 10-15 as reference value. Methionine (another one-carbon metabolism nutrient) was associated with an increased risk in men but not in women. This information cannot be used for preventive purposes in a straightforward manner.

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