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

Zhou, Ziyuan; Sturgis, Erich M; Liu, Zhensheng; Wang, Li-E; Wei, Qingyi; Li, Guojun

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

dc.contributor.author	Zhou, Ziyuan
dc.contributor.author	Sturgis, Erich M
dc.contributor.author	Liu, Zhensheng
dc.contributor.author	Wang, Li-E
dc.contributor.author	Wei, Qingyi
dc.contributor.author	Li, Guojun
dc.date.accessioned	2019-02-01T15:26:06Z
dc.date.available	2019-02-01T15:26:06Z
dc.date.issued	2012-05
dc.date.updated	2019-02-01T15:26:03Z
dc.description.abstract	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.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.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.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.
dc.identifier	1471-2407-12-159
dc.identifier.issn	1471-2407
dc.identifier.issn	1471-2407
dc.identifier.uri	https://hdl.handle.net/10161/18018
dc.language	eng
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartof	BMC cancer
dc.relation.isversionof	10.1186/1471-2407-12-159
dc.subject	Humans
dc.subject	Papillomavirus Infections
dc.subject	Carcinoma, Squamous Cell
dc.subject	Head and Neck Neoplasms
dc.subject	Proto-Oncogene Proteins c-bcl-2
dc.subject	Risk
dc.subject	Case-Control Studies
dc.subject	Age Factors
dc.subject	Genotype
dc.subject	Polymorphism, Single Nucleotide
dc.subject	Adult
dc.subject	Aged
dc.subject	Aged, 80 and over
dc.subject	Middle Aged
dc.subject	Female
dc.subject	Male
dc.subject	Human papillomavirus 16
dc.subject	Young Adult
dc.subject	Myeloid Cell Leukemia Sequence 1 Protein
dc.title	Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck.
dc.type	Journal article
duke.contributor.orcid	Wei, Qingyi\|0000-0002-3845-9445\|0000-0003-4115-4439
pubs.begin-page	159
pubs.issue	1
pubs.organisational-group	Staff
pubs.organisational-group	Duke
pubs.organisational-group	School of Medicine
pubs.organisational-group	Duke Cancer Institute
pubs.organisational-group	Institutes and Centers
pubs.organisational-group	Population Health Sciences
pubs.organisational-group	Basic Science Departments
pubs.organisational-group	Medicine, Medical Oncology
pubs.organisational-group	Medicine
pubs.organisational-group	Clinical Science Departments
pubs.publication-status	Published
pubs.volume	12

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