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

Abstract

<div>AbstractBackground:<p>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.</p>Methods:<p>African American women (<i>N</i> = 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 (<i>SDC1</i>, <i>SDC2</i>, <i>SDC3</i>, <i>SDC4</i>, <i>GPC1</i>, <i>GPC2</i>, <i>GPC3</i>, <i>GPC4</i>, <i>GPC5</i>, <i>GPC6</i>, and <i>ITGA6</i>) 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.</p>Results:<p>Minor alleles in SNPs rs77122854 (<i>SDC3</i>), rs73971695, rs79336862 (<i>ITGA6</i>), rs57528020, rs201337456, rs11987725 (<i>SDC2</i>), rs115880588, rs115738853, and rs9301825 (<i>GPC5</i>) were associated with increased odds of both CIN3+ and HSIL, whereas, rs35927186 (<i>GPC5</i>) was found to decrease the odds for both outcomes (<i>P</i> value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (<i>SDC3</i>), rs16860468, rs2356798 (<i>ITGA6</i>), rs11987725 (<i>SDC2</i>), and rs3848051 (<i>GPC5</i>) were associated with increased odds of both precancer outcomes.</p>Conclusions:<p>Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression.</p>Impact:<p>Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.</p></div>