Genetic predictors of cervical dysplasia in African American HIV-infected women: ACTG DACS 268.

Autor:	Cespedes MS; New York University School of Medicine, New York, New York., Kerns SL; Mount Sinai School of Medicine, New York, New York., Holzman RS; New York University School of Medicine, New York, New York., McLaren PJ; Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Ostrer H; Albert Einstein College of Medicine, Bronx, New York., Aberg JA; New York University School of Medicine, New York, New York.
Jazyk:	angličtina
Zdroj:	HIV clinical trials [HIV Clin Trials] 2013 Nov-Dec; Vol. 14 (6), pp. 292-302.
DOI:	10.1310/hct1406-292
Abstrakt:	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.
Databáze:	MEDLINE
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