title: Telomere Length and Neighborhood Circumstances: Evaluating Biological Response to Unfavorable Exposures.
abstract: Background:Multilevel frameworks suggest neighborhood circumstances influence biology; however, this relationship is not well studied. Telomere length (TL) shortening has been associated with individual-level and neighborhood-level exposures and disease and may provide insights into underlying biologic mechanisms linking neighborhood with biology. To support neighborhood-biology investigations, we sought to determine the independent effect of neighborhood exposures on TL using standard multilevel linear regression models and quantile regression, a nonlinear, social science method applicable for testing the biologic hypothesis that extremes of the TL distribution are related to poor outcomes.Methods:In a multicenter, cross-sectional study, blood TL was measured in 1,488 individuals from 127 census tracts in three U.S. regions using terminal restriction fragment assays. Multilevel linear and quantile regression models were adjusted for individual-level race, education, perceived stress, and depression. Neighborhood exposures included population density, urban/residential crowding, residential stability/mobility, and socioeconomic status.Results:TL was not associated with any neighborhood variable using linear models, but quantile regression revealed inverse associations between population density and urban crowding at the lower tails of the TL distribution [5th (population densityP= 0.03; urban crowdingP= 0.002), 50th (bothP< 0.001), 75th percentiles (bothP< 0.001)]. TL was related to residential stability at the upper tail (95th percentileP= 0.006).Conclusions:Findings support the use of nonlinear statistical methods in TL research and suggest that neighborhood exposures can result in biological effects.Impact:TL may serve as an underlying example of a biologic mechanism that can link neighborhood with biology, thus supporting multilevel investigations in future studies.Cancer Epidemiol Biomarkers Prev; 26(4); 553-60. ©2017 AACRSee all the articles in thisCEBP Focussection, "Geospatial Approaches to Cancer Control and Population Sciences."
authors.affiliation: Cancer Prevention and Control, Fox Chase Cancer Center, Philadelphia, Pennsylvania. shannon.lynch@fccc.edu.|Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Lynch
authors.affiliation: Cancer Prevention and Control, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
authors.affiliation: Wistar Institute, Philadelphia, Pennsylvania.
authors.forename: Krithika
authors.initials: K
authors.lastname: Ravichandran
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.|Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Elaine
authors.initials: E
authors.lastname: Spangler
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhou
authors.affiliation: The Ohio State University, Columbus, Ohio.
authors.forename: Electra D
authors.initials: ED
authors.lastname: Paskett
authors.affiliation: Washington University, St. Louis, Missouri.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gehlert
authors.affiliation: The Ohio State University, Columbus, Ohio.
authors.forename: Cecilia
authors.initials: C
authors.lastname: DeGraffinreid
authors.affiliation: Microgen Labs, La Marque, Texas.
authors.forename: Raymond
authors.initials: R
authors.lastname: Stowe
authors.affiliation: The RAND Corporation, Santa Monica, California.
authors.forename: Tamara
authors.initials: T
authors.lastname: Dubowitz
authors.affiliation: Wistar Institute, Philadelphia, Pennsylvania.|Old Dominion University, Norfolk, Virginia.
authors.forename: Harold
authors.initials: H
authors.lastname: Riethman
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Branas
authors.affiliation: University of Texas Medical Branch, Galveston, Texas.
authors.forename: M K
authors.initials: MK
authors.lastname: Peek
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania.|Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D016014:Linear Models; D012111:Residence Characteristics / Q000145:classification; D012923:Social Class; D011795:Surveys and Questionnaires; D016615:Telomere / Q000502:physiology; D059506:Telomere Shortening; D014481:United States; D014505:Urban Population
chemical_list: D015415:Biomarkers