Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Epidemiology & Biostatistics, University at Albany, State University of New York, Rensselaer, New York.
Cancer Epidemiol Biomarkers Prev. 2023 Sep 1;32(9):1190-1197. doi: 10.1158/1055-9965.EPI-23-0300.
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.
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.
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.
Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression.
Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.
宫颈癌的发生是 HPV 细胞通过与宿主细胞表面受体结合后进入细胞开始的，但具体机制尚未完全阐明。我们研究了假设对 HPV 细胞进入宿主细胞必需的受体基因的多态性，并评估了它们与癌前病变进展的相关性。
纳入 MACS/WIHS 联合队列研究中的非洲裔美国妇女（N=1728）。采用了两种病例对照研究设计，病例为组织学癌前病变（CIN3+），对照为无癌前病变；病例为细胞学癌前病变（高度鳞状上皮内病变（HSIL）），对照为无癌前病变。使用 Illumina Omni2.5-quad 珠芯片对候选基因（SDC1、SDC2、SDC3、SDC4、GPC1、GPC2、GPC3、GPC4、GPC5、GPC6 和 ITGA6）中的 SNP 进行基因分型。在调整年龄、人类免疫缺陷病毒感染状态、CD4 T 细胞和三个祖先主成分后，采用 logistic 回归评估所有参与者和 HPV 基因型的相关性。
rs77122854（SDC3）、rs73971695、rs79336862（ITGA6）、rs57528020、rs201337456、rs11987725（SDC2）、rs115880588、rs115738853 和 rs9301825（GPC5）的 SNP 中的次要等位基因与 CIN3+和 HSIL 的发生风险增加相关，而 rs35927186（GPC5）与两种结局的发生风险降低相关（P 值≤0.01）。在感染 Alpha-9 HPV 型的人群中，rs722377（SDC3）、rs16860468、rs2356798（ITGA6）、rs11987725（SDC2）和 rs3848051（GPC5）与两种癌前病变结局的发生风险增加相关。
编码 HPV 细胞进入宿主细胞的结合受体的基因多态性可能在宫颈癌前病变进展中发挥作用。
我们的发现为假说的产生提供了依据，并支持进一步探索 HPV 进入基因的作用机制，这可能有助于预防宫颈癌前病变的进展。
