Plasma One-Carbon Metabolism-Related Micronutrients and the Risk of Breast Cancer: Involvement of DNA Methylation

Findings of epidemiologic studies focusing on the association between one-carbon metabolism-related micronutrients and breast cancer risk, along with the involvement of DNA methylation, have been inconsistent and incomprehensive. We conducted a case–control study in China including 107 paired partic...

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Published inNutrients Vol. 15; no. 16; p. 3621
Main Authors Liu, Fubin, Zhou, Huijun, Peng, Yu, Qiao, Yating, Wang, Peng, Si, Changyu, Wang, Xixuan, Gong, Jianxiao, Chen, Kexin, Song, Fangfang
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.08.2023
MDPI
Subjects
Abortion
Acids
Breast cancer
Cancer
Carbon
DNA
DNA methylation
Genetic aspects
Genetic testing
Health aspects
Leaves
Mediation
Metabolism
Metabolites
Methylation
micronutrients
Oncology, Experimental
one-carbon metabolism
Physiological aspects
Plasma
Questionnaires
Risk factors
Vitamin B
China
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Summary:Findings of epidemiologic studies focusing on the association between one-carbon metabolism-related micronutrients and breast cancer risk, along with the involvement of DNA methylation, have been inconsistent and incomprehensive. We conducted a case–control study in China including 107 paired participants and comprehensively detected 12 plasma one-carbon metabolism-related micronutrients. Genomic DNA methylation was measured using an 850 K chip and differential methylation probes (DMPs) were identified. Multivariate logistic regression was performed to estimate the associations between plasma micronutrients and the odds of breast cancer. The mediation of selected DMPs in micronutrient breast cancer associations was examined using mediation analyses. An inverse association of plasma folate, methionine cycling-related micronutrients (methionine, S-adenosylmethionine, and S-adenosylhomocysteine), and all micronutrients in the choline metabolism and enzymatic factor groups, and a positive association of methionine cycling-related cysteine with breast cancer risk were observed. Nine micronutrients (methionine, cysteine, SAM, folate, choline, betaine, P5P, vitamins B2, and B12) were related to global or probe-specific methylation levels (p < 0.05). The selected DMPs mediated the micronutrient breast cancer associations with an average mediation proportion of 36.43%. This study depicted comprehensive associations between circulating one-carbon metabolism-related micronutrients and breast cancer risk mediated by DNA methylation.
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These authors contributed equally to this work.
ISSN:2072-6643
2072-6643
DOI:10.3390/nu15163621