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Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer.

ABSTRACT: Evidence suggests that cells with a stemness phenotype play a pivotal role in oncogenesis, and prostate cells exhibiting this phenotype have been identified. We used two genome-wide association study (GWAS) datasets of African descendants, from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana Prostate Study, and two GWAS datasets of non-Hispanic whites, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between genetic variants of stemness-related genes and racial disparities in susceptibility to prostate cancer. We evaluated associations of single-nucleotide polymorphisms (SNPs) in 25 stemness-related genes with prostate cancer risk in 1,609 cases and 2,550 controls of non-Hispanic whites (4,934 SNPs) and 1,144 cases and 1,116 controls of African descendants (5,448 SNPs) with correction by false discovery rate ?0.2. We identified 32 SNPs in five genes (TP63, ALDH1A1, WNT1, MET and EGFR) that were significantly associated with prostate cancer risk, of which six SNPs in three genes (TP63, ALDH1A1 and WNT1) and eight EGFR SNPs showed heterogeneity in susceptibility between these two racial groups. In addition, 13 SNPs in MET and one in ALDH1A1 were found only in African descendants. The in silico bioinformatics analyses revealed that EGFR rs2072454 and SNPs in linkage with the identified SNPs in MET and ALDH1A1 (r2 ?>?0.6) were predicted to regulate RNA splicing. These variants may serve as novel biomarkers for racial disparities in prostate cancer risk.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5512873 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer.

Wang Yanru Y Freedman Jennifer A JA Liu Hongliang H Moorman Patricia G PG Hyslop Terry T George Daniel J DJ Lee Norman H NH Patierno Steven R SR Wei Qingyi Q

International journal of cancer 20170601 4

Evidence suggests that cells with a stemness phenotype play a pivotal role in oncogenesis, and prostate cells exhibiting this phenotype have been identified. We used two genome-wide association study (GWAS) datasets of African descendants, from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana Prostate Study, and two GWAS datasets of non-Hispanic whites, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and Prostate Cancer Coh ...[more]

PMID: 28510291

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Project description:ImportanceDespite much higher health care expenditure than comparable countries, striking racial and ethnic disparities exist in obstetric outcomes in the United States. A multifaceted exploration of the factors influencing these disparities, including the legacy of structural racism, is important to improve health outcomes for all.ObjectiveTo characterize the association of the historic racially discriminatory home loan practice of redlining with disparities in modern obstetric outcomes.Design, setting, and participantsIn this retrospective cohort study of a 9-county birth certificate database in the Finger Lakes region of New York state from 2005 to 2018, modern obstetric outcomes were matched with regions classified by the federal government for mortgage loan servicing based on racially discriminatory criteria from the 1940 Home Owners' Loan Corporation map (HOLC; also known as the redline map). Patients with a live birth recorded in the data system with a recorded home zip code within the historic HOLC categories were included. Data were analyzed from July to December 2019.ExposureRegions previously categorized by historic, racially discriminatory criteria.Main outcomes and measuresEach HOLC area was analyzed for the primary outcome of preterm birth and secondary outcomes of obstetric and medical complications, with logistic regression to address regional and patient-level covariates.ResultsFrom 2005 until 2018, there were 64 804 live births within the 15 zip codes overlaying historic HOLC regions. Prevalence of preterm birth increased with decreasing HOLC categories, from the lowest overall preterm birth rate of 217 of 2873 births (7.55%) in the zip code historically defined as "Best" or "Still Desirable" and the highest overall preterm birth rate of 427 of 3449 births (12.38%) in the zip code historically defined as "Hazardous." These associations with preterm birth remained significant in logistic regression controlling for poverty levels and educational attainment (adjusted odds ratio, 1.46; 95% CI, 1.08-1.97) and parental race (adjusted odds ratio, 1.38; 95% CI, 1.25-1.53).Conclusions and relevanceIn this cohort study, the linkage of historic and modern community data sets with an obstetric data set offered the opportunity to characterize modern obstetric disparities associated with a system of historic inequity. The persistence of these findings after correcting for contemporary community socioeconomic characteristics suggest potential influences of a system of profound structural inequity that ripple forward in time, with impacts that extend beyond measurable socioeconomic inequity.

Dataset Information

Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer.

Publications

Associations between RNA splicing regulatory variants of stemness-related genes and racial disparities in susceptibility to prostate cancer.

Similar Datasets

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