Faculty Collaboration Database

Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer. Cancer Epidemiol Biomarkers Prev 2023 Sep 01;32(9):1190-1197

Date

07/06/2023

Pubmed ID

37410084

Pubmed Central ID

PMC10472094

DOI

10.1158/1055-9965.EPI-23-0300

Scopus ID

2-s2.0-85169502444 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

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 histology-based 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.

IMPACT: Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.

Author List

Mukherjee A, Ye Y, Wiener HW, Kuniholm MH, Minkoff H, Michel K, Palefsky J, D'Souza G, Rahangdale L, Butler KR, Kempf MC, Sudenga SL, Aouizerat BE, Ojesina AI, Shrestha S

Author

Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Case-Control Studies
Cohort Studies
Female
Glypicans
Humans
Papillomaviridae
Papillomavirus Infections
Polymorphism, Single Nucleotide
Uterine Cervical Dysplasia
Uterine Cervical Neoplasms