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One-Carbon Metabolism Biomarkers and Upper Gastrointestinal Cancer in the Golestan Cohort Study Publisher



Inouechoi M1 ; Freedman ND1 ; Etemadi A1 ; Hashemian M2 ; Brennan P3 ; Roshandel G4 ; Poustchi H4 ; Boffetta P5 ; Kamangar F7 ; Amiriani T4 ; Norouzi A4 ; Dawsey S1 ; Malekzadeh R8 ; Abnet CC1
Authors
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Authors Affiliations
  1. 1. Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, United States
  2. 2. Epidemiology and Community Health Branch, Division of Intramural Research, National Heart, Lung, Blood Institute, Bethesda, MD, United States
  3. 3. Genetic Section, Genomic Epidemiology, International Agency for Research on Cancer, Lyon, France
  4. 4. Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Golestan, Iran
  5. 5. Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, New York
  6. 6. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
  7. 7. Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, MD, United States
  8. 8. Digestive Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: International Journal of Cancer Published:2024


Abstract

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case–control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case–control pairs) and gastric cancer (GC; 352 case–control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99–2.04) and associated with GC (OR = 1.53, 95% CI = 1.05–2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19–3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13–2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54–5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17–3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC. © 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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