Genetic predictors of cervical dysplasia in African American HIV-infected women: ACTG DACS 268. HIV Clin Trials 2013;14(6):292-302
Date
12/18/2013Pubmed ID
24334182Pubmed Central ID
PMC4118741DOI
10.1310/hct1406-292Scopus ID
2-s2.0-84890521035 (requires institutional sign-in at Scopus site) 1 CitationAbstract
OBJECTIVE: To examine genome-wide associations in HIV-infected women with a history of cervical dysplasia compared with HIV-infected women with no history of abnormal Papanicolaou (Pap) tests.
DESIGN: Case-control study using data from women analyzed for the HIV Controllers Study and enrolled in HIV treatment-naïve studies in the AIDS Clinical Trials Group (ACTG).
METHODS: Genotyping utilized Illumina HumanHap 650 Y or 1MDuo platforms. After quality control and principal component analysis, ~610,000 significant single nucleotide polymorphisms (SNPs) were tested for association. Threshold for significance was P < 5 × 10(-8) for genome-wide associations.
RESULTS: No significant genomic association was observed between women with low-grade dysplasia and controls. The genome-wide association study (GWAS) analysis between women with high-grade dysplasia or invasive cervical cancer and normal controls identified significant SNPs. In the analyses limited to African American women, 11 SNPs were significantly associated with the development of high-grade dysplasia or cancer after correcting for multiple comparisons. The model using significant SNPs alone had improved accuracy in predicting high-grade dysplasia in African American women compared to the use of clinical data (area under the receiver operating characteristic curve for genetic and clinical model = 0.9 and 0.747, respectively).
CONCLUSIONS: These preliminary data serve as proof of concept that there may be a genetic predisposition to developing high-grade cervical dysplasia in African American HIV-infected women. Given the small sample size, the results need to be validated in a separate cohort.
Author List
Cespedes MS, Kerns SL, Holzman RS, McLaren PJ, Ostrer H, Aberg JAAuthor
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultCase-Control Studies
Female
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Genotyping Techniques
HIV Infections
Humans
Logistic Models
Middle Aged
Papanicolaou Test
Polymorphism, Single Nucleotide
Quality Control
Uterine Cervical Dysplasia
Vaginal Smears
