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

Hui-Yi Lin; Susan E Steck; Indrani Sarkar; Elizabeth T H Fontham; Alan Diekman; Lora J Rogers; Calvin T Ratliff; Jeannette T Bensen; James L Mohler; L Joseph Su

doi:10.3390/cancers15061699

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

Cancers (Basel). 2023 Mar 10;15(6):1699. doi: 10.3390/cancers15061699.

Authors

Affiliations

¹ Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
² Epidemiology and Biostatistics, and Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
³ Department of Epidemiology, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
⁴ Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
⁵ Winthrop P. Rockefeller Cancer Institute, Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
⁶ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
⁷ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁸ Department of Urology, Roswell Park Cancer Institute, Buffalo, NY 14203, USA.
⁹ Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

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.

Keywords: SNP; aggressiveness; folate metabolism; genetic variants; interaction; prostate cancer.

Abstract

Grants and funding