title: Risk of breast cancer with CXCR4-using HIV defined by V3 loop sequencing.
abstract: OBJECTIVE
  Evaluate the risk of female breast cancer associated with HIV-CXCR4 (X4) tropism as determined by various genotypic measures.
  
  
  METHODS
  A breast cancer case-control study, with pairwise comparisons of tropism determination methods, was conducted. From the Women's Interagency HIV Study repository, one stored plasma specimen was selected from 25 HIV-infected cases near the breast cancer diagnosis date and 75 HIV-infected control women matched for age and calendar date. HIV-gp120 V3 sequences were derived by Sanger population sequencing (PS) and 454-pyro deep sequencing (DS). Sequencing-based HIV-X4 tropism was defined using the geno2pheno algorithm, with both high-stringency DS [false-positive rate (3.5) and 2% X4 cutoff], and lower stringency DS (false-positive rate, 5.75 and 15% X4 cutoff). Concordance of tropism results by PS, DS, and previously performed phenotyping was assessed with kappa (κ) statistics. Case-control comparisons used exact P values and conditional logistic regression.
  
  
  RESULTS
  In 74 women (19 cases, 55 controls) with complete results, prevalence of HIV-X4 by PS was 5% in cases vs 29% in controls (P = 0.06; odds ratio, 0.14; confidence interval: 0.003 to 1.03). Smaller case-control prevalence differences were found with high-stringency DS (21% vs 36%, P = 0.32), lower stringency DS (16% vs 35%, P = 0.18), and phenotyping (11% vs 31%, P = 0.10). HIV-X4 tropism concordance was best between PS and lower stringency DS (93%, κ = 0.83). Other pairwise concordances were 82%-92% (κ = 0.56-0.81). Concordance was similar among cases and controls.
  
  
  CONCLUSIONS
  HIV-X4 defined by population sequencing (PS) had good agreement with lower stringency DS and was significantly associated with lower odds of breast cancer.
authors.affiliation: *Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD; †British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; ‡Monogram Biosciences, South San Francisco, CA; §Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY; ‖Maimonides Medical Center and State University of New York Health Sciences Center at Brooklyn, New York, NY; ¶Georgetown University School of Medicine, Washington, DC; #City of Hope National Medical Center, Duarte, CA; **Keck School of Medicine, University of Southern California, Los Angeles, CA; ††Departments of Medicine, Stroger Hospital and Rush University, Chicago, IL; ‡‡Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; §§Department of Physiological Nursing; and ‖‖The Institute for Human Genetics, University of California, San Francisco, CA; and Departments of ¶¶Clinical Pharmacy; and ##Medicine, University of California, San Francisco, CA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Luke C
authors.initials: LC
authors.lastname: Swenson
authors.forename: Laura A
authors.initials: LA
authors.lastname: Napolitano
authors.forename: Mojgan
authors.initials: M
authors.lastname: Haddad
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Alexandra
authors.initials: A
authors.lastname: Levine
authors.forename: Oluwatoyin
authors.initials: O
authors.lastname: Adeyemi
authors.forename: Eric C
authors.initials: EC
authors.lastname: Seaberg
authors.forename: Bradley
authors.initials: B
authors.lastname: Aouizerat
authors.forename: Charles S
authors.initials: CS
authors.lastname: Rabkin
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Hessol
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006678:HIV / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000235:genetics*
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4