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. 2022 Apr 29:10:834800.
doi: 10.3389/fpubh.2022.834800. eCollection 2022.

Accelerated Epigenetic Age Among Women with Invasive Cervical Cancer and HIV-Infection in Nigeria

Jonah Musa  1   2   3 , Kyeezu Kim  1 , Yinan Zheng  1   2 , Yishu Qu  1 , Brian T Joyce  1   2 , Jun Wang  1   2 , Drew R Nannini  1 , Demirkan B Gursel  2   4 , Olugbenga Silas  5 , Fatimah B Abdulkareem  6 , Godwin Imade  3 , Alani S Akanmu  7 , Jian-Jun Wei  2   4 , Masha Kocherginsky  1   2 , Kwang-Youn A Kim  1   2 , Firas Wehbe  2   8 , Chad J Achenbach  2 , Rose Anorlu  9 , Melissa A Simon  10 , Atiene Sagay  3 , Folasade T Ogunsola  11 , Robert L Murphy  2 , Lifang Hou  1   2
Affiliations

Accelerated Epigenetic Age Among Women with Invasive Cervical Cancer and HIV-Infection in Nigeria

Jonah Musa et al. Front Public Health. .

Abstract

Background: Invasive cervical cancer (ICC) is a serious public health burden in Nigeria, where human immunodeficiency virus (HIV) remains highly prevalent. Previous research suggested that epigenetic age acceleration (EAA) could play a role in detection of HIV-associated ICC. However, little research has been conducted on this topic in Africa where the population is most severely affected by HIV-associated ICC. Here, we investigated the association between ICC and EAA using cervical tissues of ICC-diagnosed Nigerian women living with HIV.

Methods: We included 116 cervical tissue samples from three groups of Nigerian women in this study: (1) HIV+/ICC+ (n = 39); (2) HIV+/ICC- (n = 53); and (3) HIV-/ICC + (n = 24). We utilized four DNA methylation-based EAA estimators; IEAA, EEAA, GrimAA, and PhenoAA. We compared EAA measurements across the 3 HIV/ICC groups using multiple linear regression models. We also compared EAA between 26 tumor tissues and their surrounding normal tissues using paired t-tests. We additionally performed a receiver operating characteristics (ROC) curve analysis to illustrate the area under the curve (AUC) of EAA in ICC.

Results: We found the most striking associations between HIV/ICC status and PhenoAge acceleration (PhenoAA). Among HIV-positive women, PhenoAA was on average 13.4 years higher in women with ICC compared to cancer-free women (P = 0.005). PhenoAA was 20.7 and 7.1 years higher in tumor tissues compared to surrounding normal tissues among HIV-positive women (P = 0.009) and HIV-negative women (P = 0.284), respectively. We did not find substantial differences in PhenoAA between HIV-positive and HIV-negative women with ICC.

Conclusion: PhenoAA is associated with ICC in HIV-infected women in our study. Our findings suggest that PhenoAA may serve as a potential biomarker for further risk stratification of HIV-associated ICC in Nigeria and similar resource-constrained settings.

Keywords: DNA methylation; LMIC; epigenetic age acceleration; human immunodeficiency virus; invasive cervical cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Area under the curve (AUC) of 4 EAA measurements from ROC curve analysis.
See this image and copyright information in PMC

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