Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer

Amrita Mukherjee, Yuanfan Ye, Howard W. Wiener, Mark H. Kuniholm, Howard Minkoff, Kate Michel, Joel Palefsky, Gypsyamber D'Souza, Lisa Rahangdale, Kenneth R. Butler, Mirjam Colette Kempf, Staci L. Sudenga, Bradley E. Aouizerat, Akinyemi I. Ojesina, Sadeep Shrestha

Research output: Contribution to journalArticlepeer-review


Background: Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer. Methods: African American women (N =1,728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used-cases with histologybased precancer (CIN3 ) and controls without; and cases with cytology-based precancer [high-grade squamous intraepithelial lesions (HSIL)] and controls without. SNPs in candidate genes (SDC1, SDC2, SDC3, SDC4, GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, and ITGA6) were genotyped using an Illumina Omni2.5-quad beadchip. Logistic regression was used to assess the associations in all participants and by HPV genotypes, after adjusting for age, human immunodeficiency virus serostatus, CD4 T cells, and three principal components for ancestry. Results: Minor alleles in SNPs rs77122854 (SDC3), rs73971695, rs79336862 (ITGA6), rs57528020, rs201337456, rs11987725 (SDC2), rs115880588, rs115738853, and rs9301825 (GPC5) were associated with increased odds of both CIN3 and HSIL, whereas, rs35927186 (GPC5) was found to decrease the odds for both outcomes (P value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (SDC3), rs16860468, rs2356798 (ITGA6), rs11987725 (SDC2), and rs3848051 (GPC5) were associated with increased odds of both precancer outcomes. Conclusions: Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression.

Original languageEnglish (US)
Pages (from-to)1190-1197
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Issue number9
StatePublished - Sep 1 2023

ASJC Scopus subject areas

  • General Medicine


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