Dataset Information

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

ABSTRACT:

Background

Both 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.

Methods

Four 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.

Results

Overall, 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.

Conclusions

Our 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.

SUBMITTER: Song X

PROVIDER: S-EPMC3574010 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

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

Song Xicheng X Sturgis Erich M EM Liu Jun J Jin Lei L Wang Zhongqiu Z Zhang Caiyun C Wei Qingyi Q Li Guojun G

PloS one 20130215 2

<h4>Background</h4>Both 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.<h4>Methods</h4>Four single-nucleotide polymorphisms in microRNAs were genotyped and HP ...[more]

PMID: 23457596

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Project description:Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is involved in the repair and prevention of uracil misincorporations into DNA. Maintenance of DNA integrity is critical for cancer prevention. Many studies have identified susceptibility loci and genetic variants in cervical cancer. The aim of this study was to explore the distribution frequency of six single nucleotide polymorphisms (SNPs) in the dUTPase-encoding gene DUT in a case-control study to identify the relationship between DUT genetic variants and cervical cancer susceptibility. Six DUT intronic SNPs (rs28381106, rs3784619, rs10851465, rs28381126, rs3784621 and rs11637235) were genotyped by mismatch amplification-PCR in 400 cervical squamous cell carcinomas (CSCCs), 400 precursor cervical intraepithelial neoplasia (CIN) III lesions and 1,200 normal controls. No correlations were found between four DUT SNPs (rs3784621, rs10851465, rs28381106 and rs28381126) and CIN III and CSCC risk. However, the homozygous GG allele of rs3784619 and TT allele of rs11637235 correlated significantly with increased risk of CIN III and CSCC (OR?=?2.29, 2.05; OR?=?3.15, 3.15, respectively). Individuals with the G allele or G carrier allele (AG?+?GG) at rs3784619 and with the T allele or T carrier allele (CT?+?TT) at rs11637235 were at higher risk for CIN III and CSCC (OR?=?1.26, 1.30; OR?=?1.41, 1.65, respectively). Similarly, in the human papillomavirus (HPV)-positive groups, we found that the homozygous GG alleles of rs3784619 and TT alleles of rs11637235 markedly increased the risk of CIN III and CSCC (OR?=?2.44, 2.71; OR?=?3.32, 4.04, respectively). When performing a stratified analysis of sexual and reproductive histories, we found that the GG genotype of rs3784619 had a particularly high level of enrichment in the group of patients with?>?one sexual partner in CIN III (P?=?0.043) and CSCC (P?=?0.007). Meanwhile, the TT genotype of rs11637235 was enriched for in the high risk HPV (HR-HPV)-positive cases of CIN III (P?=?0.033) and CSCC (P?=?0.022). Analysis of the haplotype between rs3784619 (A/G) and rs11637235 (C/T) revealed that the genotypes with AA-TT (OR?=?2.59), AG-TT (OR?=?2.29), GG-CC (OR?=?2.72), GG-CT (OR?=?3.01 (1.83-4.96)) were significantly associated with increased risk of CIN III. More notably, this risk was much greater for CSCC (AA-TT (OR?=?3.62), AG-TT (OR?=?5.08), GG-CC (OR?=?5.28), and GG-CT (OR?=?4.23). Additionally, most GG genotypes of rs3784619 were linkage GG-CT, while most TT genotypes of rs11637235 were linkage AA-TT. In conclusion, these findings suggested that the homozygous GG allele of rs3784619 and the TT allele of rs11637235 in the DUT gene significantly increased the risk of CIN III and CSCC. Most GG genotypes of rs3784619 and TT genotypes of rs11637235 were linkage GG-CT and AA-TT, respectively. The TT genotype of rs11637235 was enriched in the HR-HPV-positive cases. These two SNPs of the DUT gene can be early predictive biomarkers of CIN III and CSCC, and may be involved in HR HPV infection.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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