Common genetic variants and risk for HPV persistence and progression to cervical cancer.
HPV infrequently persists and progresses to cervical cancer. We examined host genetic factors hypothesized to play a role in determining which subset of individuals infected with oncogenic human papillomavirus (HPV) have persistent infection and further develop cervical pre-cancer/cancer compared to...
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| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008667&type=printable |
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| author | Sophia S Wang Paula Gonzalez Kai Yu Carolina Porras Qizhai Li Mahboobeh Safaeian Ana Cecilia Rodriguez Mark E Sherman Concepcion Bratti Mark Schiffman Sholom Wacholder Robert D Burk Rolando Herrero Stephen J Chanock Allan Hildesheim |
| author_facet | Sophia S Wang Paula Gonzalez Kai Yu Carolina Porras Qizhai Li Mahboobeh Safaeian Ana Cecilia Rodriguez Mark E Sherman Concepcion Bratti Mark Schiffman Sholom Wacholder Robert D Burk Rolando Herrero Stephen J Chanock Allan Hildesheim |
| author_sort | Sophia S Wang |
| collection | DOAJ |
| description | HPV infrequently persists and progresses to cervical cancer. We examined host genetic factors hypothesized to play a role in determining which subset of individuals infected with oncogenic human papillomavirus (HPV) have persistent infection and further develop cervical pre-cancer/cancer compared to the majority of infected individuals who will clear infection.We evaluated 7140 tag single nucleotide polymorphisms (SNPs) from 305 candidate genes hypothesized to be involved in DNA repair, viral infection and cell entry in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 HPV persistent women (median: 25 months), and 425 random controls (RC) from the 10,049 women Guanacaste Costa Rica Natural History study. We used logistic regression to compute odds ratios and p-trend for CIN3/cancer and HPV persistence in relation to SNP genotypes and haplotypes (adjusted for age). We obtained pathway and gene-level summary of associations by computing the adaptive combination of p-values. Genes/regions statistically significantly associated with CIN3/cancer included the viral infection and cell entry genes 2',5' oligoadenylate synthetase gene 3 (OAS3), sulfatase 1 (SULF1), and interferon gamma (IFNG); the DNA repair genes deoxyuridine triphosphate (DUT), dosage suppressor of mck 1 homolog (DMC1), and general transcription factor IIH, polypeptide 3 (GTF2H4); and the EVER1 and EVER2 genes (p<0.01). From each region, the single most significant SNPs associated with CIN3/cancer were OAS3 rs12302655, SULF1 rs4737999, IFNG rs11177074, DUT rs3784621, DMC1 rs5757133, GTF2H4 rs2894054, EVER1/EVER2 rs9893818 (p-trends</=0.001). SNPs for OAS3, SULF1, DUT, and GTF2H4 were associated with HPV persistence whereas IFNG and EVER1/EVER2 SNPs were associated with progression to CIN3/cancer. We note that the associations observed were less than two-fold. We identified variations DNA repair and viral binding and cell entry genes associated with CIN3/cancer. Our results require replication but suggest that different genes may be responsible for modulating risk in the two critical transition steps important for cervical carcinogenesis: HPV persistence and disease progression. |
| format | Article |
| id | doaj-art-c2c1b4e9ea234ca7bf20d70d54fe1f1d |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c2c1b4e9ea234ca7bf20d70d54fe1f1d2025-08-20T03:07:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e866710.1371/journal.pone.0008667Common genetic variants and risk for HPV persistence and progression to cervical cancer.Sophia S WangPaula GonzalezKai YuCarolina PorrasQizhai LiMahboobeh SafaeianAna Cecilia RodriguezMark E ShermanConcepcion BrattiMark SchiffmanSholom WacholderRobert D BurkRolando HerreroStephen J ChanockAllan HildesheimHPV infrequently persists and progresses to cervical cancer. We examined host genetic factors hypothesized to play a role in determining which subset of individuals infected with oncogenic human papillomavirus (HPV) have persistent infection and further develop cervical pre-cancer/cancer compared to the majority of infected individuals who will clear infection.We evaluated 7140 tag single nucleotide polymorphisms (SNPs) from 305 candidate genes hypothesized to be involved in DNA repair, viral infection and cell entry in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 HPV persistent women (median: 25 months), and 425 random controls (RC) from the 10,049 women Guanacaste Costa Rica Natural History study. We used logistic regression to compute odds ratios and p-trend for CIN3/cancer and HPV persistence in relation to SNP genotypes and haplotypes (adjusted for age). We obtained pathway and gene-level summary of associations by computing the adaptive combination of p-values. Genes/regions statistically significantly associated with CIN3/cancer included the viral infection and cell entry genes 2',5' oligoadenylate synthetase gene 3 (OAS3), sulfatase 1 (SULF1), and interferon gamma (IFNG); the DNA repair genes deoxyuridine triphosphate (DUT), dosage suppressor of mck 1 homolog (DMC1), and general transcription factor IIH, polypeptide 3 (GTF2H4); and the EVER1 and EVER2 genes (p<0.01). From each region, the single most significant SNPs associated with CIN3/cancer were OAS3 rs12302655, SULF1 rs4737999, IFNG rs11177074, DUT rs3784621, DMC1 rs5757133, GTF2H4 rs2894054, EVER1/EVER2 rs9893818 (p-trends</=0.001). SNPs for OAS3, SULF1, DUT, and GTF2H4 were associated with HPV persistence whereas IFNG and EVER1/EVER2 SNPs were associated with progression to CIN3/cancer. We note that the associations observed were less than two-fold. We identified variations DNA repair and viral binding and cell entry genes associated with CIN3/cancer. Our results require replication but suggest that different genes may be responsible for modulating risk in the two critical transition steps important for cervical carcinogenesis: HPV persistence and disease progression.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008667&type=printable |
| spellingShingle | Sophia S Wang Paula Gonzalez Kai Yu Carolina Porras Qizhai Li Mahboobeh Safaeian Ana Cecilia Rodriguez Mark E Sherman Concepcion Bratti Mark Schiffman Sholom Wacholder Robert D Burk Rolando Herrero Stephen J Chanock Allan Hildesheim Common genetic variants and risk for HPV persistence and progression to cervical cancer. PLoS ONE |
| title | Common genetic variants and risk for HPV persistence and progression to cervical cancer. |
| title_full | Common genetic variants and risk for HPV persistence and progression to cervical cancer. |
| title_fullStr | Common genetic variants and risk for HPV persistence and progression to cervical cancer. |
| title_full_unstemmed | Common genetic variants and risk for HPV persistence and progression to cervical cancer. |
| title_short | Common genetic variants and risk for HPV persistence and progression to cervical cancer. |
| title_sort | common genetic variants and risk for hpv persistence and progression to cervical cancer |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008667&type=printable |
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