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

Publication ,  Journal Article
Zhou, Z; Sturgis, EM; Liu, Z; Wang, L-E; Wei, Q; Li, G
Published in: BMC Cancer
May 1, 2012

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.

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Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

May 1, 2012

Volume

12

Start / End Page

159

Location

England

Related Subject Headings

  • Young Adult
  • Squamous Cell Carcinoma of Head and Neck
  • Risk
  • Proto-Oncogene Proteins c-bcl-2
  • Polymorphism, Single Nucleotide
  • Papillomavirus Infections
  • Oncology & Carcinogenesis
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Middle Aged
  • Male
 

Citation

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Zhou, Z., Sturgis, E. M., Liu, Z., Wang, L.-E., Wei, Q., & Li, G. (2012). Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck. BMC Cancer, 12, 159. https://doi.org/10.1186/1471-2407-12-159
Zhou, Ziyuan, Erich M. Sturgis, Zhensheng Liu, Li-E Wang, Qingyi Wei, and Guojun Li. “Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck.BMC Cancer 12 (May 1, 2012): 159. https://doi.org/10.1186/1471-2407-12-159.
Zhou Z, Sturgis EM, Liu Z, Wang L-E, Wei Q, Li G. Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck. BMC Cancer. 2012 May 1;12:159.
Zhou, Ziyuan, et al. “Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck.BMC Cancer, vol. 12, May 2012, p. 159. Pubmed, doi:10.1186/1471-2407-12-159.
Zhou Z, Sturgis EM, Liu Z, Wang L-E, Wei Q, Li G. Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck. BMC Cancer. 2012 May 1;12:159.
Journal cover image

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

May 1, 2012

Volume

12

Start / End Page

159

Location

England

Related Subject Headings

  • Young Adult
  • Squamous Cell Carcinoma of Head and Neck
  • Risk
  • Proto-Oncogene Proteins c-bcl-2
  • Polymorphism, Single Nucleotide
  • Papillomavirus Infections
  • Oncology & Carcinogenesis
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Middle Aged
  • Male