Dataset Information

The interaction between smoking status and highly active antiretroviral therapy (HAART) use on the risk of Kaposi's sarcoma (KS) in a cohort of HIV-infected men.

ABSTRACT: Although the independent effects of smoking status and HAART are reported as lower risks against KS, their combined effects have not been explored. We examined whether there is an interaction between smoking status and HAART use on the risk of KS development in an on-going US cohort of HIV-infected men.Cox proportional hazards regression was used to analyse a total sample of 2736 participants of the Multicenter AIDS Cohort Study (MACS).We identified 530 incident KS cases with a total follow-up time of 26?594 person-years (incidence rate: 2.00 out of 100 person-years). Current smoking status and HAART use were independently associated with a lower risk of KS development (hazard ratio - HR=0.56, 95% CI: 0.35-0.90, P=0.02 and HR=0.27, 95% CI: 0.16-0.48, P<0.0001, respectively). There was no evidence of multiplicative interaction between current smoking status and HAART use on KS risk (HR=2.14, 95% CI: 0.97-4.73, Pinteraction=0.06). Lower effect of smoking was only present among those not on HAART (HR=0.57, 95% CI: 0.35-0.92, P=0.02).The inverse association of cigarette smoking on KS risk may be limited to those not on HAART. The biological mechanism of smoking in KS carcinogenesis should be elucidated.

SUBMITTER: Luu HN

PROVIDER: S-EPMC3619085 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

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The interaction between smoking status and highly active antiretroviral therapy (HAART) use on the risk of Kaposi's sarcoma (KS) in a cohort of HIV-infected men.

Luu H N HN Amirian E S ES Scheurer M E ME

British journal of cancer 20130219 5

<h4>Background</h4>Although the independent effects of smoking status and HAART are reported as lower risks against KS, their combined effects have not been explored. We examined whether there is an interaction between smoking status and HAART use on the risk of KS development in an on-going US cohort of HIV-infected men.<h4>Methods</h4>Cox proportional hazards regression was used to analyse a total sample of 2736 participants of the Multicenter AIDS Cohort Study (MACS).<h4>Results</h4>We identi ...[more]

PMID: 23422755

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Project description:In sub-Saharan Africa, endemic Kaposi's sarcoma (EnKS) is still prevalent despite high incidence of epidemic Kaposi's sarcoma (EpKS) resulting from the on-going HIV-1 epidemic. While KSHV is clearly the etiologic agent of KS, the mechanisms underlying KS development are not fully understood. For example, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in EpKS remains unclear. How, or whether, EpKS is mechanistically distinct from EnKS is unknown. Thus, the absence of HIV-1 co-infection in EnKS provides a unique control for investigating and deciphering whether HIV-1 plays a direct or indirect role in the EpKS tumor microenvironment. We hypothesized that HIV-1 co-infection would induce transcriptome changes that differentiate EpKS from EnKS, thereby defining the direct intra-tumor role of HIV-1 in KS. Comparison of ART-treated and -naïve patients would further define the impact of ART on the KS transcriptome. We utilized RNA-seq followed by multiparameter bioinformatics analysis to compare transcriptomes from KS lesions to uninvolved control skin. We provide the first transcriptomic comparison of EpKS versus EnKS, ART-treated vs-naïve EpKS and male vs female EpKS to define the roles of HIV-1 co-infection, the impact of ART, and gender on KS gene expression profiles. Our findings suggest that ART-use and gender have minimal impact on transcriptome profiles of KS lesions. Gene expression profiles strongly correlated between EpKS and EnKS patients (Spearman r = 0.83, p<10-10). A subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude, but not unique dysregulation in EnKS compared to EpKS. While gender and ART had no detectable contribution, the trend toward higher magnitude of gene dysregulation in EnKS coupled with the absence of HIV-1 transcripts in EpKS may suggest an indirect or systemic effect of HIV-1 to promote KS tumorigenesis.

Dataset Information

The interaction between smoking status and highly active antiretroviral therapy (HAART) use on the risk of Kaposi's sarcoma (KS) in a cohort of HIV-infected men.

Publications

The interaction between smoking status and highly active antiretroviral therapy (HAART) use on the risk of Kaposi's sarcoma (KS) in a cohort of HIV-infected men.

Similar Datasets

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