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Association of genetic variants with tumor HPV16 status and survival in squamous cell carcinoma of the oropharynx.

Abstract：

OBJECTIVES:Genetic polymorphisms of genes in cell cycle, apoptosis, and inflammation/immune response pathways may control the mechanisms of HPV clearance and HPV escape of immune surveillance and thus may affect both tumor HPV16 status and possibly related outcomes of squamous cell carcinoma of the oropharynx (SCCOP) patients. MATERIALS AND METHODS:We determined tumor HPV16 status and genotyped selected polymorphisms in key genes involved in cell cycle, apoptosis, and inflammation/immune response pathways in 401 incident SCCOP patients. Unconditional logistic regression models, Kaplan-Meier analysis, and Cox proportional hazards regression were used to evaluate associations and survival. RESULTS:Compared to the corresponding common homozygous genotypes, the variant genotypes of genes in cell cycle (p53, p73, MDM2, p16), apoptosis (CASP8, and Fas), and inflammation/immune response pathways (IL1β and IL10) were significantly associated with HPV16-positive tumors among SCCOP patients. In HPV16-positive SCCOP patients only, compared to those with the corresponding common homozygous genotypes, patients with variant genotypes of p53 (119G>C), MDM2 (309T>G), p16 (580C>T), Fas (1377G>A), and IL1β (14T>C) had significantly better overall survival, and approximately 40-70% reduced or 5-fold increased risk of overall death, respectively, after adjustment for important prognostic confounders. Moreover, the combined adverse genotypes of 5 variants were also significantly associated with reduced risk of overall death of HPV16-positive SCCOP. CONCLUSION:These results suggest that genetic polymorphisms in likely functional regions of the genes in these pathways may individually or, more likely, jointly affect individual susceptibility to HPV16 tumor status and constitute the confounding effect on HPV16-related clinical outcomes. Validation of our findings is warranted.

journal_name

Oral Oncol

journal_title

Oral oncology

authors

Feng Y,Li Y,Zhang Y,Zheng H,Li G

doi

10.1016/j.oraloncology.2016.03.012

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

78-83

eissn

1368-8375

issn

1879-0593

pii

S1368-8375(16)30005-7

journal_volume

56

pub_type

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