Abstract
The increasing incidence of squamous cell carcinoma of the oropharynx (SCCOP) is majorly attributed to the human papillomavirus (HPV) infection. Both HPV and MDM4 play a critical role in inhibition of p53 activity, thus affecting HPV tumor status of SCCOP. Three polymorphisms in MDM4 were genotyped from blood genomic DNA samples and HPV16 status in tumor specimens was examined. Odds ratio (OR) and 95% confidence intervals (CIs) in univariate and multivariable logistic regression models were calculated for the associations between these polymorphisms and HPV16 status. Three MDM4 variant genotypes were significantly associated with HPV16 tumor status among SCCOP patients compared with the common homozygous genotypes (OR, 0.6; 95% CI, 0.4–1.0 for rs10900598; OR, 1.6, 95% CI; 1.1–2.4 for rs1380576; and OR, 1.8, 95% CI, 1.1–2.9 for rs11801299; respectively). When we combined all risk genotypes of the 3 polymorphisms, the patients carrying 1-3 MDM4 risk genotypes were approximately 2.5 time as likely to have an HPV16-positive tumor than those with no risk genotypes (OR, 2.5, 95% CI, 1.6–3.9). Additionally, modifying effect of MDM4 risk genotypes was more pronounced among non-Hispanic white, never-smokers, and never-drinkers. Potential functional polymorphisms in MDM4 may serve as biomarkers for predicting tumor HPV16 status among SCCOP patients, particularly in non-Hispanic white, never-smokers and never-drinkers. However, validation of these results in larger studies is needed.
Highlights
The majority of SCC of head and neck (SCCHN) are contributed to tobacco and alcohol use
A significant association between the three Mouse double minute 4 (MDM4) polymorphisms and HPV16 tumor status in patients with squamous cell carcinoma of the oropharynx (SCCOP) were found; and such associations were more pronounced among some subgroups
This result indicates that these MDM4 genetic variants might have potential to be biomarkers for HPV16posoitive tumors of SCCOP, in the patients who were younger, non-smokers, and non-drinkers
Summary
The majority of SCCHN are contributed to tobacco and alcohol use. Squamous cell carcinoma of the oropharynx (SCCOP), one of subgroups of SCC of head and neck (SCCHN), has recently become one of the only five cancer types that are growing significantly in incidence regardless of the www.impactjournals.com/oncotarget VariableAge ≤54 years >54 years Sex Male Female Ethnicity Non-Hispanic white Others Tobacco smoking Ever Never Alcohol drinking Ever NeverHPV16+ patients (N =439) No.HPV16- patients (N =113)P value* 0.856 0.0012 0.141 0.050 0.483 decline in smoking rate in the United States [1]. The majority of SCCHN are contributed to tobacco and alcohol use. Age ≤54 years >54 years Sex Male Female Ethnicity Non-Hispanic white Others Tobacco smoking Ever Never Alcohol drinking Ever Never. Human papillomavirus (HPV) infection has been well established as the principal cause for the increased incidence of SCCOP [1,2,3,4,5,6,7]. HPV16-positive SCCOP has been widely recognized to be a distinct disease and has better treatment outcome compared with HPV16-negative SCCOP [9, 10]. Besides HPV infection, as a necessary but not a sufficient cause of SCCOP, other factors, such as genetic factors, may be necessary in malignant transformation of HPV infected cells
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