Abstract 4297: Serum B6 vitamers (pyridoxal-5’-phosphate, pyridoxal, and 4’-pyridoxic acid) and pancreatic cancer risk: Two nested case-control studies in Asian populations

Abstract

Abstract Background: Vitamin B6 is an important enzymatic cofactor in the synthesis of one-carbon units, amino acids, and carbohydrates. Epidemiological studies provided inconsistent results on the associations between circulating pyridoxal 5’-phosphate (PLP) and pancreatic cancer risk. Method: Two nested case-control studies were conducted within the Shanghai Cohort Study (SCS) (129 cases and 258 matched controls) and the Singapore Chinese Health Study (SCHS) (58 cases and 104 matched controls). Concentrations of B6 vitamers [PLP, pyridoxal (PL), and pyridoxic acid (PA)] were measured in serum samples that were collected an average of 12.5 years in SCS and 6.8 years in SCHS before pancreatic cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with the adjustment for potential confounders. Restricted cubic splines were used to explore potential non-linear relationships between serum B6 vitamer levels and pancreatic cancer risk. Results: The median (5th-95th percentiles) levels of serum PLP were 25.7 (10.0-91.7) nmol/L among SCS controls and 58.1 (20.8-563.0) nmol/L among SCHS controls. There was a statistically significant inverse association between serum PLP levels and pancreatic cancer risk in SCS [comparing highest (&gt35.6 nmol/L) with lowest quartile (&lt18.1 nmol/L): OR = 0.44; 95%CI: 0.21, 0.91; P for trend = 0.01]. A weaker, nonsignificant association was observed in SCHS [comparing highest (&gt88.2 nmol/L) with lowest quartile (&lt39.2 nmol/L): OR = 0.78; 95%CI: 0.27, 2.25; P for trend = 0.64]. We combined the data from the two cohorts for the purpose of estimating the serum PLP-pancreatic cancer association using the widest PLP range available. Compared with PLP < 20 nmol/L (defined as vitamin B6 deficiency), PLP ≥ 45 nmol/L was associated with 50% reduced risk of pancreatic cancer (OR = 0.50; 95%CI: 0.26, 0.97). Although the linear trend test was statistically significant (P = 0.04), the spline curve modeling revealed a non-linear relationship between serum PLP and pancreatic cancer, where the strongest inverse relationship was seen among individuals with serum PLP of below approximately 30 nmol/L, while a weak association was seen for those with higher PLP levels. The inverse association between PLP and pancreatic cancer risk remained statistically significant after excluding cases whose blood samples were collected within 2 years prior to cancer diagnosis. No statistically significant association was found between serum level of PL or PA and pancreatic cancer risk. Conclusion: This study is consistent with the notion that higher circulating levels of PLP may protect against the development of pancreatic cancer. The inverse association between circulating PLP and pancreatic cancer risk may be masked in studies without a wide range of PLP levels, or enough subjects in deficient range. Citation Format: Joyce Y. Huang, Lesley M. Butler, Øivind Midttun, Per M. Ueland, Woon-Puay Koh, Yu-Tang Gao, Jian-Min Yuan. Serum B6 vitamers (pyridoxal-5’-phosphate, pyridoxal, and 4’-pyridoxic acid) and pancreatic cancer risk: Two nested case-control studies in Asian populations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4297.