Vitamin B12 may play a preventive role in esophageal precancerous lesions: a case–control study based on markers in blood and 3-day duplicate diet samples



It is hypothesized that vitamin B12 may prevent tumor initiation during the early stage of carcinogenesis such as esophageal precancerous lesions (EPL), whereas an excessive level may promote tumor progression during the later stages of carcinogenesis. This study aimed to determine the role of vitamin B12 in EPL by detecting vitamin B12-related markers in both blood and diet.


This case–control study based on 3-day duplicated diet samples was conducted in a high-risk area of Huai'an, China. A 100 EPL cases and 100 healthy controls matched by gender, age (± 2 years) and villages were included. Dietary intake of vitamin B12 and cobalt, plasma cobalt level, the serum levels of vitamin B12 and transcobalamin II (TC II) were quantitatively analyzed.


Dietary vitamin B12 intake (p for trend = 0.384) and plasma cobalt level (p for trend = 0.253) were not associated with EPL risk, but high dietary cobalt intake (p for trend = 0.034), increased serum levels of vitamin B12 (p for trend = 0.036) and TC II (p for trend < 0.001) were significantly associated with the reduced EPL risk. However, the significant negative association between dietary cobalt intake, plasma cobalt level or serum vitamin B12 level and EPL was only found in female or male subjects.


Excellent transport capability of bio-active vitamin B12 in vivo and adequate levels of vitamin B12 and cobalt may play preventive roles in EPL. Additionally, the association between vitamin B12, cobalt and the risk of EPL may vary in different genders.

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Fig. 1
Fig. 2

Availability of data and material

All data generated or analyzed during this study are included.

Code availability

The technical appendix and statistical procedure are available from the corresponding author.



Body mass index


Confidence: interval


Dietary history questionnaire


Esophageal adenocarcinoma


Esophageal cancer


Early Diagnosis and Early Treatment Project of Esophageal Cancer


Enzyme-linked immunosorbent assay


Esophageal precancerous lesion


Esophageal squamous cell carcinoma


Food frequency questionnaire


5,10-Methylenetetrahydrofolate reductase


Optical density


Odds ratio


Transcobalamin II


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We thank all the participants, researchers and collaborators who were involved in the study for their efforts and contribution. Thanks to Dr. Ying Zhang for providing technical guidance on methods for ICP-MS. Thanks also to Mr Rob Unwin for proof reading. This research was supported by the National Natural Science Foundation of China (No. 81673147), Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX20_0063) and the Danone Dietary Nutrition Research and Education Foundation (DIC2020-08). The funding unit had no role in the whole study including study design, collection of data, and analysis of results and composition of the manuscript.


This research was supported by the National Natural Science Foundation of China (No. 81673147), Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX20_0063) and the Danone Dietary Nutrition Research and Education Foundation (DIC2020-08). The funding unit had no role in the whole study including study design, collection of data, analysis of results, and composition of the manuscript.

Author information




DP, SW, and GS designed research; DP, MS, XZ, MGC, ZG, NW, and ZZ conducted research; SW, MS, MC, and GS provided essential materials; DP analyzed data; DP wrote paper; SW had primary responsibility for final content. All authors read and approved the final manuscript.

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Correspondence to Shaokang Wang.

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The study was approved by the Institutional Review Board of Southeast University Zhongda Hospital, in accordance with the Declaration of Helsinki.

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Written informed consent was obtained from each subject.

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Pan, D., Wang, S., Su, M. et al. Vitamin B12 may play a preventive role in esophageal precancerous lesions: a case–control study based on markers in blood and 3-day duplicate diet samples. Eur J Nutr (2021).

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  • Vitamin B12
  • Cobalt
  • Transcobalamin II
  • Esophageal precancerous lesions
  • Duplicate diet