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Interactions Between Obesity and One-Carbon Metabolism Genes in Predicting Prostate Cancer Outcomes Among White and Black Patients

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Abstract

Background

One-carbon metabolism genes are linked to several cancers, but the association with prostate cancer (PCa) is less clear. Studies examining the relationship have not accounted for obesity, a risk factor for advanced PCa and altered methylation patterns. We hypothesized that obesity could moderate the association between one-carbon metabolism genes and PCa outcomes.

Methods

We conducted secondary data analyses of the Study of Clinical Outcomes, Risk and Ethnicity. Obesity was included as a primary exposure and modifier (interacting with genetic polymorphisms) in the analytic models. We used logistic regression to determine associations of common one-carbon metabolism genotypes with odds of high stage (T3/T4) and high grade (Gleason score ≥ 7). We used Cox regression to examine associations of genotypes with biochemical recurrence.

Results

There were 808 patients (632 White and 176 Black.) Among White men, we observed associations of TCN2_R259P with increased odds of high stage (OR = 0.64, 95% CI = 0.41–1.00), but no significant interactions with obesity. Among Black men, the SCL19A1_61bpdel and CBS_68bpINS variants were associated with high grade (OR = 2.61, 95% CI = 1.39–4.89 and OR = 0.29, 95% CI = 0.09–0.91, respectively.) Both the CBS_68bpINS and MTHFR_E429A variants interacted with obesity in Black men, where the highest risk for biochemical failure and odds of high grade, respectively, occurred among obese patients with variants.

Conclusions

We observed associations of one-carbon metabolism genes with different associations by race. We also observed interactions with obesity related to PCa outcomes in Black men only. Therefore, the involvement of one-carbon metabolism on PCa was dependent upon obesity status for Black men. These novel results could help identify patients that might benefit from effective weight management targeting one-carbon metabolism effects.

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Data Availability

Data can be obtained by contacting the corresponding author or director of the SCORE Study, Dr. Timothy Rebbeck (Harvard University).

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Acknowledgments

We would like to thank Dr. Timothy R. Rebbeck (Dana Farber Cancer Institute) for providing access to data from the SCORE study.

Funding

This study was funded by the Pennsylvania (PA) Department of Health. However, the PA Department of Health did not play a role in the study design, analysis, interpretation of results, or writing of the manuscript.

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Authors and Affiliations

  1. Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA

    Scott W. Keith

  2. Department of Biochemistry and Molecular Biology, Howard University, Washington, DC, USA

    Bernard Kwabi-Addo

  3. Division of Population Science, Department of Medical Oncology, Thomas Jefferson University, Suite 314, 834 Chestnut Street, Philadelphia, PA, 19107, USA

    Charnita Zeigler-Johnson

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Contributions

SK assisted with drafting the manuscript, data analysis and interpretation, and manuscript revisions.

BKA contributed to the manuscript draft and revisions.

CZJ acquired data, was responsible for the study concept/design, analysis, and interpretation, and drafted the manuscript.

Corresponding author

Correspondence to Charnita Zeigler-Johnson.

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The authors declare that they have no conflicts of interest.

Ethics Approval and Consent to Participate

This observational study based upon secondary data analysis of the Study of Clinical Outcomes, Risk and Ethnicity (SCORE) was approved by the Institutional Review Board (IRB) at Thomas Jefferson University (Philadelphia, PA). The IRB reference number is 16S.256. Informed consent was waived by the review board.

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Keith, S.W., Kwabi-Addo, B. & Zeigler-Johnson, C. Interactions Between Obesity and One-Carbon Metabolism Genes in Predicting Prostate Cancer Outcomes Among White and Black Patients. J. Racial and Ethnic Health Disparities 9, 305–314 (2022). https://doi.org/10.1007/s40615-020-00958-6

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