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E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.

ABSTRACT: Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1?008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P?

SUBMITTER: Li Y

PROVIDER: S-EPMC6036627 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.

Li Yuncheng Y Sturgis Erich M EM Zhu Lijun L Cao Xiaoli X Wei Qingyi Q Zhang Hua H Li Guojun G

Molecular carcinogenesis 20170102 4

Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous ...[more]

PMID: 27864908

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| S-EPMC5689719 | biostudies-literature

Interleukin-10 promoter variants predict HPV-positive tumors and survival of squamous cell carcinoma of the oropharynx.

Project description:Interleukin-10 (IL-10) plays an important role in a host's defense against human papillomavirus (HPV) infection. IL-10 promoter variants may affect its expression level or functional efficiency and, subsequently, susceptibility to and survival of HPV16-associated squamous cell carcinoma of oropharynx (SCCOP). We determined tumor HPV16 DNA and genotyped three IL-10 promoter polymorphisms in 309 incident patients with SCCOP. Compared with the patients with corresponding common homozygous genotypes, patients carrying variant genotypes of IL-10 rs1800871 and rs1800872 were ~2.5 times more likely to have HPV16(+) tumors among patients with SCCOP. Among HPV16(+) patients with SCCOP only, compared to those with the corresponding variant genotypes, the patients with IL-10 rs1800871 and rs1800872 CC genotypes had significantly better survival and ~70-80% reduced risk of death/recurrence after multivariable adjustment. Additionally, functional relevance of these variants was characterized to explore the genotype-phenotype correlation. Our findings indicate that IL-10 genetic variants may be associated with tumor HPV16(+) SCCOP and predict survival of HPV16(+) patients with SCCOP. Larger studies are needed to validate our findings.

| S-EPMC3659362 | biostudies-literature

MicroRNA variants increase the risk of HPV-associated squamous cell carcinoma of the oropharynx in never smokers.

Project description:BackgroundBoth microRNAs and human papillomavirus (HPV) infection play an important role in the development and progression of oral squamous cell carcinoma (OSCC). In addition, microRNAs affect all facets of the immune/inflammation responses to infection, which may control HPV clearance. We thus hypothesized that microRNA polymorphisms modify the association between HPV16 seropositivity and OSCC risk.MethodsFour single-nucleotide polymorphisms in microRNAs were genotyped and HPV16 serology was determined in 325 cases and 335 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariable logistic regression models.ResultsOverall, each polymorphism had no significant main effect on OSCC risk. Compared with the risk among individuals with both miR146 rs2910164 GG genotype and HPV16 seronegativity, risk of OSCC was increased among those with CG or CC genotype and HPV16 seronegativity (OR, 1.2; 95% CI, 0.9-1.8), GG genotype and HPV16 seropositivity (OR, 3.0; 95% CI, 1.8-5.0), and CG or CC genotype and HPV16 seropositivity (OR, 4.7; 95% CI, 2.3-9.4). Similar results were found for miR149 rs2292832, miR196 rs11614913, and miR499 rs3746444. Analyses stratified by tumor sites and smoking status showed that each polymorphism significantly increased the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly prominent in never smokers.ConclusionsOur results indicate that microRNA polymorphisms modify the risk of OSCC associated with HPV16 seropositivity, particularly in patients with SCCOP and never smokers. Larger studies are needed to verify our findings.

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Project description:To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor specimens and genotyped four SNPs in pre-miRNAs (hsa-mir-146a rs2910164 G>C, hsa-mir-149 rs2292832 G>T, hsa-mir-196a2 rs11614913 C>T, and hsa-mir-499 rs3746444 A>G) in 309 SCCOP patients. Unconditional logistic regression models were used for calculation of odds ratio (OR) and 95% confidence intervals (CIs), and Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate associations. We found that statistically significant associations with HPV16-positive SCCOP and survival were found for hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913, while such similar associations were not observed for hsa-mir-149 rs2292832 and hsa-mir499 rs3746444. Compared with those with corresponding hsa-mir-146a CG/CC and has-mir-196a2 CC genotypes, the hsa-mir-146a GG and hsa-mir-196a2 CT/TT wild-type genotypes were significantly associated with HPV16-positive tumor status (adjusted OR, 2.4; 95% CI, 1.4-4.1 and adjusted OR, 2.1, 95% CI, 1.2-3.6), respectively. Patients having hsa-mir-146a rs2910164 GG and hsa-mir196a2 rs11614913 CT/TT genotypes had significantly better overall, disease-specific, and disease-free survival compared with those having the corresponding CG/CC and CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders including HPV status, smoking, and stage. Our findings indicate pre-miRNA polymorphisms may predict tumor HPV16-positive SCCOP cases and may be prognostic biomarkers for SCCOP.

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