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

dc.contributor.author Liu, Zhensheng
dc.contributor.author Wei, Qingyi
dc.contributor.author Zhou, Ziyuan
dc.contributor.author Sturgis, Erich M
dc.contributor.author Wang, Li-E
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.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.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.language eng
dc.publisher Springer Nature
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
dc.date.updated 2019-02-01T15:26:03Z
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
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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