Related Experiment Video
Updated: Jun 9, 2026

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Context-dependent effects of genome-wide association study genotypes and macroenvironment on time to biochemical
Timothy R Rebbeck1, Anita L Weber, Amy H Walker
1Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, 217 Blockley Hall, 423 Guardian Drive, Philadelphia, Pennsylvania 19104-6021, USA. rebbeck@mail.med.upenn.edu
Background:
Disparities in cancer defined by race, age, or gender are well established. However, demographic metrics are surrogates for the complex contributions of genotypes, exposures, health care, socioeconomic and sociocultural environment, and many other factors. Macroenvironmental factors represent novel surrogates for exposures, lifestyle, and other factors that are difficult to measure but might influence cancer outcomes.
Methods:
We applied a "multilevel molecular epidemiology" approach using a prospective cohort of 444 White prostate cancer cases who underwent prostatectomy and were followed until biochemical failure (BF) or censoring without BF. We applied Cox regression models to test for joint effects of 86 genome-wide association study-identified genotypes and macroenvironment contextual effects after geocoding all cases to their residential census tracts. All analyses were adjusted for age at diagnosis and tumor aggressiveness.
Results:
Residents living in census tracts with a high proportion of older single heads of household, high rates of vacant housing, or high unemployment had shorter time until BF postsurgery after adjustment for patient age and tumor aggressiveness. After correction for multiple testing, genotypes alone did not predict time to BF, but interactions predicting time to BF were observed for MSMB (rs10993994) and percentage of older single heads of households (P = 0.0004), and for HNF1B/TCF2 (rs4430796) and census tract per capita income (P = 0.0002).
Conclusions:
The context-specific macroenvironmental effects of genotype might improve the ability to identify groups that might experience poor prostate cancer outcomes.
Impact:
Risk estimation and clinical translation of genotype information might require an understanding of both individual- and macroenvironment-level context.
Related Concept Videos
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Background and Environment Affect Phenotype
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
