Higher Serum Levels of Pyridoxal-5’-Phosphate Associated with Reduced Risk of Colorectal Cancer

by | Aug 17, 2022 | 2022, Cancer, Colorectal (Colon), Vitamin B6

Written by Taylor Woosley, Staff Writer. Results of the large-scale case-control study show that the sum of PL and PLP were significantly associated with the risk of CRC. Comparing the highest with the lowest quartile, the adjusted ORs (95% CI) were 0.26 (0.20-0.33, Ptrend < 0.001) for serum PLP and 0.51 (0.40-0.66, Ptrend < 0.001) for PL plus PLP. 

colon cancerColorectal cancer (CRC) is the second most common cause of death worldwide and by 2030, the global burden of CRC will increase by 60%, with the number of deaths exceeding 1.1 million1. Despite CRC screening programs, including fecal testing and colonoscopy, CRC still has a high incidence and mortality rate2. It has been reported that CRC originates from a combination of genetic, environmental, and behavioral risk factors3. A variety of modifiable lifestyle risk factors, including excess adiposity, physical inactivity, high intake of red and/or processed meat, alcohol consumption, and smoking are closely linked to CRC incidence4.

Several B-vitamins and related nutrients have been studied in relation to CRC risk, with higher plasma concentration levels of pyridoxal 5’-phosphate being associated with lower CRC risk5. Vitamin B6 is a strong antioxidant and a key coenzyme involved in amino acid, lipid, and glucose metabolism6. The physiologically active form of vitamin B6, pyridoxal 5’-phosphate (PLP), is an essential cofactor for hundreds of human enzymes that are involved in diverse cellular processes7.

Xu et al. conducted a large-scale case-control study to evaluate the association of vitamin B6 with colorectal cancer risk. Subjects (n=1233) were of Chinese descent between ages 30-75 years, who were histologically diagnosed with CRC within the last 3 months of the start of the study. Participants (n=1841) in the first control group, who were free of any cancers, were frequency matched to CRC subjects based on age and sex. The second control group featured community-derived subjects (n=934). All participants completed interviews centered on their sociodemographic characteristics, lifestyle habits, body height and weight, and history of cancer in first-degree relatives. For female subjects, information on age at menarche and menopausal status was collected.

Blood samples were drawn from participants, with serum B6 biomarkers, including PLP, PL, and PA being detected using high-performance liquid chromatography-tandem mass spectrometry. The Student’s t-test or Wilcoxon signed-rank test was utilized to examine continuous variables between the differences in demographic characteristics between cases and control subjects, with use of the X2 test for categorical variables. To estimate odds ratio (OR) and 95% confidence intervals (CI), an unconditional logistic regression was used to analyze the relationship between serum concentrations of each vitamin B6 biomarker and the CRC risk after adjusting for potential confounders. Serum PLP concentrations and the sum of PL plus PLP were categorized into quartiles (Q1-Q4) based on the distribution among controls for males and females, separately. Significant findings of the large-scale case-control study are as follows:

  • Serum levels of PLP and the sum of PL and PLP were significantly inversely associated with CRC risk. Comparing the highest with the lowest quartile, the adjusted ORs (95% CI) were 0.26 (0.20-0.33, Ptrend < 0.001) for serum PLP and 0.51 (0.40-0.66, Ptrend < 0.001) for PL plus PLP. Serum PAr values were significantly associated with an increased risk of colorectal cancer, with an adjusted ORs (95% Cis) of 2.90 (2.25-3.75, Ptrend < 0.001) for the highest versus the lowest quartile.
  • Sex-stratified analysis showed similar inverse associations between serum PL plus PLP and CRC risk in both sexes, but the inverse association between serum PLP and CRC risk was stronger in males than females (Pinteraction = 0.001). Furthermore, the positive association of PAr with CRC risk was stronger in males than in females (Pinteraction = 0.001).
  • A subgroup analysis by cancer site showed that serum PLP, and PL plus PLP levels were inversely associated with the risk of both colon cancer and rectal cancer (P for heterogeneity > 0.05).

Study findings show that serum PLP and the sum of PL plus PLP level were inversely associated with CRC risk. Additionally, results show a significant positive association between serum PAr and CRC risk. Future studies should include a variety of vitamin B6 biomarkers to assess other potential factors in CRC risk. Study limitations include selection bias due to the study design and the use of a single measurement which cannot observe the long-term circulating levels of biomarkers.

Source: Lei Xu , Yu-Jing Fang, Meng-Meng Che, Alinuer Abulimiti, Chu-Yi Huang and Cai-Xia Zhang, Association of Serum Pyridoxal-50 -Phosphate, Pyridoxal, and PAr with Colorectal Cancer Risk: A Large-Scale Case-Control Study, Nutrients 2022, 14, 2389.

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Click here to read the full text study.

Posted August 17, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

  1. Zhang Z, Zhang Y, Lao S, Qiu J, Pan Z, Feng X. The clinicopathological and prognostic significances of IGF-1R and Livin expression in patients with colorectal cancer. BMC Cancer. Aug 5 2022;22(1):855. doi:10.1186/s12885-022-09961-y
  2. Kim N, Gim JA, Lee BJ, et al. Crosstalk between mucosal microbiota, host gene expression, and sociomedical factors in the progression of colorectal cancer. Sci Rep. Aug 4 2022;12(1):13447. doi:10.1038/s41598-022-17823-7
  3. Gholamalizadeh M, Majidi N, Tajaddod S, et al. Interactions of Colorectal Cancer, Dietary Fats, and Polymorphisms of Arachidonate Lipoxygenase and Cyclooxygenase Genes: A Literature Review. Front Oncol. 2022;12:865208. doi:10.3389/fonc.2022.865208
  4. Yu J, Feng Q, Kim JH, Zhu Y. Combined Effect of Healthy Lifestyle Factors and Risks of Colorectal Adenoma, Colorectal Cancer, and Colorectal Cancer Mortality: Systematic Review and Meta-Analysis. Front Oncol. 2022;12:827019. doi:10.3389/fonc.2022.827019
  5. Gylling B, Myte R, Ulvik A, et al. One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk. Int J Cancer. Mar 1 2019;144(5):947-956. doi:10.1002/ijc.31606
  6. Palacios N, Scott T, Sahasrabudhe N, Gao X, Tucker KL. Lower Plasma Vitamin B-6 is Associated with 2-Year Cognitive Decline in the Boston Puerto Rican Health Study. J Nutr. Apr 1 2019;149(4):635-641. doi:10.1093/jn/nxy268
  7. He S, Chen Y, Wang L, et al. Structural and Functional Analysis of the Pyridoxal Phosphate Homeostasis Protein YggS from Fusobacterium nucleatum. Molecules. Jul 26 2022;27(15)doi:10.3390/molecules27154781