Frontiers in Public Health (Apr 2022)

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

  • Jonah Musa,
  • Jonah Musa,
  • Jonah Musa,
  • Kyeezu Kim,
  • Yinan Zheng,
  • Yinan Zheng,
  • Yishu Qu,
  • Brian T. Joyce,
  • Brian T. Joyce,
  • Jun Wang,
  • Jun Wang,
  • Drew R. Nannini,
  • Demirkan B. Gursel,
  • Demirkan B. Gursel,
  • Olugbenga Silas,
  • Fatimah B. Abdulkareem,
  • Godwin Imade,
  • Alani S. Akanmu,
  • Jian-Jun Wei,
  • Jian-Jun Wei,
  • Masha Kocherginsky,
  • Masha Kocherginsky,
  • Kwang-Youn A. Kim,
  • Kwang-Youn A. Kim,
  • Firas Wehbe,
  • Firas Wehbe,
  • Chad J. Achenbach,
  • Rose Anorlu,
  • Melissa A. Simon,
  • Atiene Sagay,
  • Folasade T. Ogunsola,
  • Robert L. Murphy,
  • Lifang Hou,
  • Lifang Hou

DOI
https://doi.org/10.3389/fpubh.2022.834800
Journal volume & issue
Vol. 10

Abstract

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BackgroundInvasive 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.MethodsWe 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.ResultsWe 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.ConclusionPhenoAA 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.

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