Possible Combined Effects of Plasma Folate Levels, Global DNA Methylation, and Blood Cadmium Concentrations on Renal Cell Carcinoma

Chao-Yuan Huang; Wei-Jen Chen; Hui-Ling Lee; Ying-Chin Lin; Ya-Li Huang; Horng-Sheng Shiue; Yeong-Shiau Pu; Yu-Mei Hsueh

doi:10.3390/nu15040937

Possible Combined Effects of Plasma Folate Levels, Global DNA Methylation, and Blood Cadmium Concentrations on Renal Cell Carcinoma

Nutrients. 2023 Feb 13;15(4):937. doi: 10.3390/nu15040937.

Authors

Chao-Yuan Huang¹, Wei-Jen Chen², Hui-Ling Lee³, Ying-Chin Lin^{4

5

6}, Ya-Li Huang⁷, Horng-Sheng Shiue⁸, Yeong-Shiau Pu¹, Yu-Mei Hsueh^{4

7}

Affiliations

¹ Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei City 110, Taiwan.
² Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
³ Department of Chemistry, Fu Jen Catholic University, New Taipei City 242, Taiwan.
⁴ Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City 110, Taiwan.
⁵ Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 110, Taiwan.
⁶ Department of Occupational Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City 110, Taiwan.
⁷ Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 110, Taiwan.
⁸ Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan.

Abstract

Epigenetic effects of environmental pollutants may be related to carcinogenesis. This study aimed to explore the association between the global DNA methylation marker: 5-methyl-2-deoxycytidine (5mdC) and renal cell carcinoma (RCC), and further investigated whether plasma folate and vitamin B₁₂ levels and 5mdC modified the association between blood cadmium concentrations and RCC. We recruited 174 RCC patients and 673 non-RCC controls. Blood cadmium concentrations, plasma folate and vitamin B₁₂ levels were measured. The amount of 5mdC in the DNA sample was expressed as percentages of the total cytosine content. An increase of 5mdC (%) and plasma folate and vitamin B₁₂ levels were associated with decreasing odds ratio (OR) of RCC. Although plasma folate levels were not directly associated with 5mdC (%), a combined effect was observed with the odds of low plasma folate levels and low 5mdC (%) were greater among RCC patients compared to controls (OR (95% confidence interval, CI) = 11.86 (5.27-26.65)). Additionally, we observed that the odds of low plasma folate and high blood cadmium levels were greater among RCC patients than in controls (OR (95% CI): 8.15 (1.39-7.13)). This study provides suggestive evidence that plasma folate levels may modify the associations between 5mdC (%) or blood cadmium concentrations and RCC.

Keywords: 5-Methyl-2-deoxycytidine; cadmium; folate; renal cell carcinoma; vitamin B12.

MeSH terms

Cadmium
Carcinoma, Renal Cell*
Case-Control Studies
DNA Methylation
Folic Acid
Homocysteine
Humans
Kidney Neoplasms*
Vitamin B 12
Vitamins

Substances

Cadmium
Folic Acid
Vitamin B 12
Vitamins
Homocysteine

Grants and funding

This study was supported by grants from the Ministry of Science and Technology of the Republic of China (MOST 106-2314-B-038-066, MOST 107-2320-B-039-010, MOST 106-2314-B-002-235-MY3, MOST 107-2314-B-038-073, MOST 108-2314-B-038-089, MOST 109-2314-B-038-081, MOST 109-2314-B-038-067, MOST 110-2314-B-038-054, MOST 110-2314-B-002-113, MOST 111-2314-B-038-052, and MOST 111-2314-B-002-240-MY3).