Association of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer: the Japan Public Health Center-based (JPHC) prospective study

Paramita Khairan,Ling Zha,Ehab Salah Eshak,Shoichiro Tsugane,Tetsuhisa Kitamura,Taichi Shimazu,Taiki Yamaji,Motoki Iwasaki,Norie Sawada,Tomotaka Sobue,Manami Inoue,Hiroyasu Iso

doi:10.1186/s12885-021-08721-8

Paramita Khairan, Ling Zha + Show 10 more

Open Access

https://doi.org/10.1186/s12885-021-08721-8

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Abstract

BackgroundB vitamins and methionine are essential substrates in the one-carbon metabolism pathway involved in DNA synthesis and methylation. They may have essential roles in cancer development. We aimed to evaluate the associations of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer (EC) using data from the Japan Public Health Center-based Prospective Study.MethodsWe included 87,053 Japanese individuals who completed a food frequency questionnaire and were followed up from 1995–1998 to 2013 and 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox proportional-hazard regression across quintiles of dietary intakes of B vitamins and methionine.ResultsAfter 1,456,678 person-years of follow-up, 427 EC cases were documented. The multivariable HR (95% CI) of incident EC in the highest versus lowest quintile of dietary intake of vitamin B12 was 1.75 (1.13–2.71; p-trend=0.01). Stratification analysis based on alcohol consumption showed that higher dietary intakes of vitamin B12 and methionine were associated with an increased risk of EC among never-drinkers; HRs (95% CIs) were 2.82 (1.18–6.74; p-trend=0.009; p-interaction=0.18) and 3.45 (1.32–9.06; p-trend=0.003; p-interaction 0.02) for vitamin B12 and methionine, respectively. Meanwhile, there was no association between vitamin B12 and methionine intake with the risk of EC among drinkers. There were no associations between dietary intake of folate or vitamin B6 and the risk of EC.ConclusionDietary intake of vitamin B12 was positively associated with the risk of EC in the Japanese population.

Highlights

B vitamins and methionine are essential substrates in the one-carbon metabolism pathway involved in DNA synthesis and methylation
The positive association between vitamin B12 intake and risk of esophageal cancer (EC) became stronger after further adjustment for vitamin B6, folate, and methionine (Model 3; Hazard ratio (HR) and 95% Confidence interval (CI): 1.75 [1.132.71]; p-trend =0.01)
After excluding EC cases diagnosed within three years of enrolment, the association did not alter materially (Model 3: HR and 95% CI: 1.74[1.09–2.78]; p-trend =0.02)

Summary

Introduction

B vitamins and methionine are essential substrates in the one-carbon metabolism pathway involved in DNA synthesis and methylation. They may have essential roles in cancer development. Esophageal squamous cell carcinomas account for 88% of EC cases, with an increasing trend of incidence among women in several countries, including Japan [2]. Lifestyle habits such as alcohol consumption and tobacco smoking are the main risk factors for esophageal squamous cell carcinoma [3]. Vitamin B12 and folate are the primary components of the one-carbon metabolism (OCM) pathway involved in DNA synthesis, repair, and methylation [7, 8]. A dietary imbalance or deficiency in those nutrients may disrupt DNA methylation or induce the disincorporation of nucleotide synthesis, which could lead to carcinogenesis [9]

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