West African Genetic Ancestry, Neighborhood Deprivation, and Prostate Cancer

Abstract

Importance: Racial disparities in prostate cancer are likely the result of complex relationships between both socioeconomic and environmental factors captured by the neighborhood environment and genetic factors, including West African genetic ancestry. However, few studies have examined the combined role of neighborhood environment and genetic ancestry in developing lethal prostate cancer.

Objective: To examine the interactions between West African genetic ancestry and neighborhood deprivation in modifying prostate cancer risk and mortality.

Design, setting, and participants: This case-control study was conducted in the Greater Baltimore area. Participants included men of African and European descent (617 cases with prostate cancer, 852 controls without prostate cancer) enrolled between January 2005 and January 2016. Follow-up was performed through December 31, 2020, using the National Death Index. Analysis was conducted from August 2023 to January 2024.

Exposure: Included exposures were West African genetic ancestry, derived from large-scale genotyping, and neighborhood deprivation, defined using 2000 census-tract-level Neighborhood Deprivation Index (NDI) score.

Main outcomes and measures: Outcomes of interest were prostate cancer and all-cause mortality.

Results: Among a total of 1469 participants (mean [SD] age, 64.96 [7.95] years), there were 736 self-identified Black and 733 White men, and the mean (range) proportion of West African genetic ancestry was 0.27 (0.04-0.84) among participants residing in areas with low levels of deprivation and 0.48 (0.07-0.83) among participants residing in areas with high levels of deprivation. Multivariable logistic regression analysis revealed a significant multiplicative interaction of West African genetic ancestry and neighborhood deprivation with the odds of a prostate cancer diagnosis (P for interaction = .02). Among individuals living in neighborhoods with high NDI scores, West African genetic ancestry was associated with increased odds of a prostate cancer diagnosis (age-adjusted odds ratio [OR], 1.98; 95% CI, 1.23-3.19). In contrast, West African genetic ancestry was associated with reduced odds of this diagnosis among individuals residing in areas with medium to low levels of deprivation (age-adjusted OR, 0.22; 95% CI, 0.11-0.44). There was no significant multiplicative interaction between West African genetic ancestry and neighborhood deprivation for all-cause mortality (P for interaction = .44). The positive association of neighborhood deprivation with prostate cancer was independent of West African genetic ancestry (age- and West African ancestry-adjusted OR, 1,70; 95% CI, 1.50-1.94).

Conclusions and relevance: This case-control study of men with West African and European ancestry found that West African genetic ancestry was associated with increased odds of prostate cancer among males who resided in neighborhoods with high deprivation but lower odds in more affluent neighborhoods. Thus, neighborhood environments may play a critical role in defining how genetic ancestry modulates prostate cancer risk.

Figure.. Association of West African Ancestry and Neighborhood Deprivation Index With a Prostate Cancer Diagnosis and All-Cause Mortality

A, Odds ratios (OR) and 95% CIs for the association of either West African ancestry or neighborhood deprivation with a prostate cancer diagnosis. B, Hazard ratios (HRs) and 95% CIs for the association of either West African ancestry or neighborhood deprivation with all-cause mortality. Model 1 is unadjusted. Model 2 is age-adjusted. Model 3 adjusts for age and Neighborhood Deprivation Index (NDI) with West African ancestry as the exposure or for age and West African ancestry with NDI as the exposure. Mortality models are additionally adjusted for National Comprehensive Cancer Network risk score categories (low, intermediate, high or very high, and regional or metastatic), current body mass index (continuous), and smoking status (never, former, current, or missing). C, Association of West African ancestry with a prostate cancer diagnosis and all-cause mortality when stratified by NDI. Prostate cancer diagnosis is reported as OR and all-cause mortality as HR. NDI was dichotomized at the median (≤median vs >median). West African ancestry was estimated using 55 446 genotyped single nucleotide variations.