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

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.