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Open Access Research article

Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck

Ziyuan Zhou1, Erich M Sturgis12, Zhensheng Liu1, Li-E Wang1, Qingyi Wei1 and Guojun Li123*

Author Affiliations

1 Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

2 Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

3 Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

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BMC Cancer 2012, 12:159  doi:10.1186/1471-2407-12-159

Published: 1 May 2012

Abstract

Background

The cooperation between phorbol 12-myristate 13-acetate induced protein 1 (NOXA) and myeloid cell leukemia 1 (MCL1) is critical in the intrinsic apoptotic pathway. Human papillomavirus 16 (HPV16), by inducing p53 and pRb-E2F degradation, may play an essential role in development of squamous cell carcinoma of the head and neck (SCCHN) through NOXA-MCL1 axis-mediated apoptosis. Therefore, genetic variants of NOXA and MCL1 may modify the SCCHN risk associated with HPV16 seropositivity.

Methods

HPV16 serology was obtained by immunoadsorption assay. Four functional SNPs in the promoter of NOXA (rs9957673, rs4558496) and MCL1 (rs9803935, rs3738485) were genotyped for 380 cases and 335 frequency-matched cancer-free controls of non-Hispanic whites.

Results

Associations between the four polymorphisms and SCCHN risk were not significant, while we observed a significantly joint effect on SCCHN risk between the polymorphisms and HPV16 seropositivity. Notably, this effect modification was particularly pronounced for oropharyngeal cancer in subgroups including never smokers, never drinkers and younger subjects.

Conclusions

Our results suggested that polymorphisms of NOXA and MCL1 may modify the risk of HPV16-associated oropharyngeal cancer. The further identification of population subgroups at higher risk provides evidence that HPV-targeting treatment may help benefit SCCHN. However, larger studies are needed to validate our findings.

Keywords:
NOXA; MCL1; HPV16; Genetic susceptibility; Squamous cell carcinoma of the head and neck