Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Pre-Cancer
Menée auprès de 1 728 Afro-Américaines et à l'aide de données d'études sur l'histologie du cancer du col de l'utérus, cette étude analyse l'association entre des polymorphismes à simple nucléotide dans les gènes récepteurs supposés permettre l'entrée des cellules du papillomavirus humain (HPV) et une infection persistante par le HPV ou la survenue de lésions précancéreuses
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 pre-cancer.
Methods: African-American women (N=1728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used - cases with histology-based pre-cancer (CIN3+) and controls without; and cases with cytology-based pre-cancer (HSIL) and controls without. Single nucleotide polymorphisms (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, HIV-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 pre-cancer outcomes.
Conclusions: Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical pre-cancer progression.
Impact: Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical pre-cancer.
Cancer Epidemiology, Biomarkers & Prevention , article en libre accès, 2022