通过V3环测序定义的使用CXCR4的HIV感染者患乳腺癌的风险。

Risk of breast cancer with CXCR4-using HIV defined by V3 loop sequencing.

作者信息

Goedert James J, Swenson Luke C, Napolitano Laura A, Haddad Mojgan, Anastos Kathryn, Minkoff Howard, Young Mary, Levine Alexandra, Adeyemi Oluwatoyin, Seaberg Eric C, Aouizerat Bradley, Rabkin Charles S, Harrigan P Richard, Hessol Nancy A

机构信息

*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.

出版信息

J Acquir Immune Defic Syndr. 2015 Jan 1;68(1):30-5. doi: 10.1097/QAI.0000000000000400.

DOI:10.1097/QAI.0000000000000400

PMID:25321183

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4262599/

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.

摘要

目的

评估通过各种基因型检测方法确定的与HIV-CXCR4（X4）嗜性相关的女性乳腺癌风险。

方法

开展了一项乳腺癌病例对照研究，对嗜性确定方法进行成对比较。从妇女机构间HIV研究资料库中，在乳腺癌诊断日期附近从25例HIV感染病例中选取一份储存的血浆标本，并从75名年龄和日历日期匹配的HIV感染对照女性中选取一份。通过桑格群体测序（PS）和454焦磷酸深度测序（DS）获得HIV-gp120 V3序列。基于测序的HIV-X4嗜性使用geno2pheno算法定义，包括高严格度DS[假阳性率（3.5）和2% X4临界值]以及低严格度DS（假阳性率5.75和15% X4临界值）。用kappa（κ）统计评估PS、DS和先前进行的表型分析的嗜性结果一致性。病例对照比较采用确切P值和条件逻辑回归。

结果

在74名有完整结果的女性（19例病例，55名对照）中，PS检测的HIV-X4患病率在病例组中为5%，在对照组中为29%（P = 0.06；比值比，0.14；置信区间：0.003至1.03）。高严格度DS（21%对36%，P = 0.32）、低严格度DS（16%对35%，P = 0.18）和表型分析（11%对31%，P = 0.10）的病例对照患病率差异较小。PS和低严格度DS之间的HIV-X4嗜性一致性最佳（93%，κ = 0.83）。其他成对一致性为82%-92%（κ = 0.56-0.81）。病例组和对照组之间的一致性相似。