DNA methylation and dietary sodium intake
Principal Investigator
Name
Constanza Camargo
Degrees
PhD
Institution
National Cancer Institute
Position Title
Senior Investigator
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-1950
Initial CDAS Request Approval
Aug 12, 2025
Title
DNA methylation and dietary sodium intake
Summary
This project will investigate the association between dietary sodium intake and blood cell DNA methylation within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial cohort. High sodium intake has been consistently linked to adverse health outcomes, including cardiovascular disease and gastric cancer. However, the molecular mechanisms underlying these associations remain incompletely understood. Epigenetic modifications, particularly DNA methylation, represent a potential pathway through which dietary sodium may influence gene expression and cellular function, ultimately contributing to disease pathogenesis.
This study will investigate the relationship between dietary sodium intake and blood cell DNA methylation profiles within the PLCO cohort. We will analyze previously generated data on approximately 8,000 participants.(1-6) White blood cell (WBC) DNA methylation was measured by next generation sequencing of bisulfite modified DNA. This research has the potential to identify novel epigenetic signatures linked to dietary sodium intake and to elucidate biological pathways by which excess sodium may contribute to chronic disease.
References
1. Huang WY, Su LJ, Hayes RB, Moore LE, Katki HA, Berndt SI, Weissfeld JL, Yegnasubramanian S, Purdue MP. Prospective study of genomic hypomethylation of leukocyte DNA and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):2014-21.
2. Karami S, Andreotti G, Liao LM, Pfeiffer RM, Weinstein SJ, Purdue MP, Hofmann JN, Albanes D, Mannisto S, Moore LE. LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk. Epigenetics. 2015;10(4):282-92.
3. Sturgeon SR, Pilsner JR, Arcaro KF, Ikuma K, Wu H, Kim SM, Chopra-Tandon N, Karpf AR, Ziegler RG, Schairer C, Balasubramanian R, Reckhow DA. White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Breast Cancer Res. 2017 Aug 18;19(1):94.
4. Sturgeon SR, Sela DA, Browne EP, Einson J, Rani A, Halabi M, Kania T, Keezer A, Balasubramanian R, Ziegler RG, Schairer C, Kelsey KT, Arcaro KF. Prediagnostic White Blood Cell DNA Methylation and Risk of Breast Cancer in the Prostate Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort. Cancer Epidemiol Biomarkers Prev. 2021 Aug;30(8):1575-1581.
5. Gao L, Zhang Z, Cui XL, West-Szymanski D, Ye C, He C, Zhang W, Bissonnette M. Analysis of genome-wide 5-hydroxymethylation of blood samples stored in different anticoagulants: opportunities for the expansion of clinical resources for epigenetic research. Epigenetics. 2023 Dec;18(1):2271692.
6. Vermeulen R, Bodinier B, Dagnino S, Wada R, Wang X, Silverman D, Albanes D, Freedman N, Rahman M, Bell D, Chadeau-Hyam M, Rothman N. A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer. Eur J Epidemiol. 2024 Apr;39(4):393-407.
This study will investigate the relationship between dietary sodium intake and blood cell DNA methylation profiles within the PLCO cohort. We will analyze previously generated data on approximately 8,000 participants.(1-6) White blood cell (WBC) DNA methylation was measured by next generation sequencing of bisulfite modified DNA. This research has the potential to identify novel epigenetic signatures linked to dietary sodium intake and to elucidate biological pathways by which excess sodium may contribute to chronic disease.
References
1. Huang WY, Su LJ, Hayes RB, Moore LE, Katki HA, Berndt SI, Weissfeld JL, Yegnasubramanian S, Purdue MP. Prospective study of genomic hypomethylation of leukocyte DNA and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):2014-21.
2. Karami S, Andreotti G, Liao LM, Pfeiffer RM, Weinstein SJ, Purdue MP, Hofmann JN, Albanes D, Mannisto S, Moore LE. LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk. Epigenetics. 2015;10(4):282-92.
3. Sturgeon SR, Pilsner JR, Arcaro KF, Ikuma K, Wu H, Kim SM, Chopra-Tandon N, Karpf AR, Ziegler RG, Schairer C, Balasubramanian R, Reckhow DA. White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Breast Cancer Res. 2017 Aug 18;19(1):94.
4. Sturgeon SR, Sela DA, Browne EP, Einson J, Rani A, Halabi M, Kania T, Keezer A, Balasubramanian R, Ziegler RG, Schairer C, Kelsey KT, Arcaro KF. Prediagnostic White Blood Cell DNA Methylation and Risk of Breast Cancer in the Prostate Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort. Cancer Epidemiol Biomarkers Prev. 2021 Aug;30(8):1575-1581.
5. Gao L, Zhang Z, Cui XL, West-Szymanski D, Ye C, He C, Zhang W, Bissonnette M. Analysis of genome-wide 5-hydroxymethylation of blood samples stored in different anticoagulants: opportunities for the expansion of clinical resources for epigenetic research. Epigenetics. 2023 Dec;18(1):2271692.
6. Vermeulen R, Bodinier B, Dagnino S, Wada R, Wang X, Silverman D, Albanes D, Freedman N, Rahman M, Bell D, Chadeau-Hyam M, Rothman N. A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer. Eur J Epidemiol. 2024 Apr;39(4):393-407.
Aims
Primary Aim. To characterize the association between dietary sodium intake, as measured by Frequency Questionnaires, and genome-wide DNA methylation patterns in White blood cell samples. Data from multiple sets within PLCO will be combined via fixed-effects meta-analysis. Heterogeneity will be assessed using I2 statistics and Cochran’s Q. We will use linear regression models to examine the association between sodium intake (continuous and categorical variables) and DNA methylation levels at individual CpG sites and across genomic regions. Covariables such as age, sex, body mass index, smoking status, and other relevant factors will be included in the models to control for potential confounding.
Collaborators
To be determined.