RESUMEN
The association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer. Blood levels of circulating fatty acids vary significantly between the three population groups, particularly trans, omega-3 and omega-6 fatty acids. FADS1/2 germline genetic variants and lifestyle factors explain some of the variation in fatty acid levels, with the FADS1/2 locus showing population-specific associations, suggesting differences in their control by germline genetic factors. All trans fatty acids, namely elaidic, palmitelaidic, and linoelaidic acids, associated with an increase in the odds of developing prostate cancer, independent of ancestry, geographic location, or potential confounders.
Asunto(s)
Ácidos Grasos Omega-3 , Neoplasias de la Próstata , Ácidos Grasos trans , Masculino , Humanos , Estados Unidos/epidemiología , Ghana/epidemiología , Ácido Graso Desaturasas/genética , Ácidos Grasos , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Importance: Neighborhood variables may be factors in the excessive burden of prostate cancer among African American men. Objective: To examine associations between neighborhood deprivation, circulating immune-oncology markers, and prostate cancer among African American and European American men. Design, Setting, and Participants: A case-control study was conducted between January 1, 2005, and January 1, 2016. Participants included men with prostate cancer and age- and race-frequency-matched population controls. Participants were recruited at the Baltimore Veterans Affairs Medical Center and University of Maryland Medical Center; controls were obtained through the Maryland Motor Vehicle Administration database. National Death Index follow-up was performed through December 31, 2020, and data analysis was conducted from February 1, 2022, through October 31, 2022. Exposures: 2000 Census-tract Neighborhood Deprivation Index as a standardized score. Main Outcomes and Measures: Primary outcomes included prostate cancer, all-cause mortality, and disease-specific mortality. Secondary outcomes included the National Comprehensive Cancer Network risk score and serum proteomes for 82 immune-oncology markers with pathway annotation. Results: Participants included men with prostate cancer (n = 769: 405 African American, 364 European American men) and age- and race-frequency-matched population controls (n = 1023: 479 African American, 544 European American men). The median survival follow-up was 9.70 years (IQR, 5.77 years), with 219 deaths. Among 884 African American men, mean (SD) age at recruitment was 63.8 (7.6) years; mean (SD) age at recruitment among 908 European American men was 66.4 (8.1) years. In the multivariable logistic regression analysis with individual socioeconomic status adjustment, neighborhood deprivation was associated with 55% increased odds of prostate cancer among African American men (odds ratio [OR], 1.55; 95% CI, 1.33-1.81), but was not associated with the disease among European American men. Residing in the most-deprived vs least-deprived neighborhoods corresponded to 88% higher disease odds (OR, 1.88; 95% CI, 1.30-2.75) among all men and an approximate 3-fold increase among African American men (OR, 3.58; 95% CI, 1.72-7.45), but no association was noted among European American men. In Cox proportional hazard regression analyses, socioeconomic status-adjusted neighborhood deprivation was associated with an increased all-cause mortality only among African American men (hazard ratio [HR], 1.28; 95% CI, 1.08-1.53), whereas it was associated with metastatic disease and a 50% increased hazard of a prostate cancer-specific death among all men (HR, 1.50; 95% CI, 1.07-2.09). In analyses restricted to controls, neighborhood deprivation was associated with increased activity scores of serum proteome-defined chemotaxis, inflammation, and tumor immunity suppression. Conclusions and Relevance: The findings of this study suggest that deprived neighborhood residency may increase the risk of African American men for prostate cancer and a related mortality, potentially through its association with systemic immune function and inflammation.