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

Keith, Scott W.; Kwabi-Addo, Bernard; Zeigler‐Johnson, Charnita

doi:10.1007/s40615-020-00958-6

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…For example, the frequency of polymorphisms in DHFR and MTHFR genes differs by race, and associations between polymorphisms and circulating folate levels also vary by race [ 43 , 44 , 45 , 46 , 47 , 48 ]. In addition, some SNPs in one-carbon metabolism genes are significantly associated with high-grade PCa in white and black men, but these associations differ by race [ 49 ]. Furthermore, we are interested in two more genes: LGALS3 and SLC4A5 .…”

Section: Introductionmentioning

confidence: 99%

Interactions of SNPs in Folate Metabolism Related Genes on Prostate Cancer Aggressiveness in European Americans and African Americans

Lin

Steck

Sarkar

et al. 2023

Cancers

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Background: Studies showed that folate and related single nucleotide polymorphisms (SNPs) could predict prostate cancer (PCa) risk. However, little is known about the interactions of folate-related SNPs associated with PCa aggressiveness. The study’s objective is to evaluate SNP–SNP interactions among the DHFR 19-bp polymorphism and 10 SNPs in folate metabolism and the one-carbon metabolism pathway associated with PCa aggressiveness. Methods: We evaluated 1294 PCa patients, including 690 European Americans (EAs) and 604 African Americans (AAs). Both individual SNP effects and pairwise SNP–SNP interactions were analyzed. Results: None of the 11 individual polymorphisms were significant for EAs and AAs. Three SNP–SNP interaction pairs can predict PCa aggressiveness with a medium to large effect size. For the EA PCa patients, the interaction between rs1801133 (MTHFR) and rs2236225 (MTHFD1), and rs1801131 (MTHFR) and rs7587117 (SLC4A5) were significantly associated with aggressive PCa. For the AA PCa patients, the interaction of DHFR-19bp polymorphism and rs4652 (LGALS3) was significantly associated with aggressive PCa. Conclusions: These SNP–SNP interactions in the folate metabolism-related genes have a larger impact than SNP individual effects on tumor aggressiveness for EA and AA PCa patients. These findings can provide valuable information for potential biological mechanisms of PCa aggressiveness.

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Section: Introductionmentioning

confidence: 99%

Interactions of SNPs in Folate Metabolism Related Genes on Prostate Cancer Aggressiveness in European Americans and African Americans

Lin

Steck

Sarkar

et al. 2023

Cancers

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“…AA men often are diagnosed at an earlier age and present at an advanced grade and stage of disease than their EA counterparts [ 2 ]. While many socioeconomic and environmental factors contribute to these disparities, there is evidence of biological differences in the tumors of AA and EA PCa patients, particularly in tumor metabolism and genomic instability [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Our lab previously identified DNA repair as a top gene signature enriched in AA compared to EA across a pan-cancer gene set enrichment analysis (GSEA) of TCGA data [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Repair-Assisted Damage Detection Reveals Biological Disparities in Prostate Cancer between African Americans and European Americans

Krieger

Gohlke

Lee

et al. 2022

Cancers

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African Americans (AA) are two times more likely to be diagnosed with and succumb to prostate cancer (PCa) compared to European Americans (EA). There is mounting evidence that biological differences in these tumors contribute to disparities in patient outcomes. Our goal was to examine the differences in DNA damage in AA and EA prostate tissues. Tissue microarrays with matched tumor-benign adjacent pairs from 77 AA and EA PCa patients were analyzed for abasic sites, oxidative lesions, crosslinks, and uracil content using the Repair Assisted Damage Detection (RADD) assay. Our analysis revealed that AA PCa, overall, have more DNA damage than EA PCa. Increased uracil and pyrimidine lesions occurred in AA tumors, while EA tumors had more oxidative lesions. AA PCa have higher levels of UMP and folate cycle metabolites than their EA counterparts. AA PCa showed higher levels of UNG, the uracil-specific glycosylase, than EA, despite uracil lesions being retained within the genome. AA patients also had lower levels of the base excision repair protein XRCC1. These results indicate dysfunction in the base excision repair pathway in AA tumors. Further, these findings reveal how metabolic rewiring in AA PCa drives biological disparities and identifies a targetable axis for cancer therapeutics.

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Obesity and biochemical recurrence in clinically localised prostate cancer: a systematic review and meta-analysis of 86,490 patients

Rivera-Izquierdo

Rojas

Martínez-Ruiz

et al. 2022

Prostate Cancer Prostatic Dis

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

Cited by 3 publications

References 38 publications

Interactions of SNPs in Folate Metabolism Related Genes on Prostate Cancer Aggressiveness in European Americans and African Americans

Interactions of SNPs in Folate Metabolism Related Genes on Prostate Cancer Aggressiveness in European Americans and African Americans

Repair-Assisted Damage Detection Reveals Biological Disparities in Prostate Cancer between African Americans and European Americans

Obesity and biochemical recurrence in clinically localised prostate cancer: a systematic review and meta-analysis of 86,490 patients

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