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Genetic variants of a BH3-only pro-apoptotic gene, PUMA, and 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: Mol Carcinog
October 2012

P53 up-regulated modulator of apoptosis (PUMA) is a critical factor in the intrinsic apoptotic pathway. Through PUMA-dependent mechanisms, human papillomavirus 16 (HPV16) oncoprotein may affect apoptosis by E6-mediated p53 degradation. To examine whether the PUMA variants modify the association between HPV16 serology and risk of squamous cell carcinoma of the head and neck (SCCHN), we genotyped two polymorphisms in the PUMA promoter (rs3810294 and rs2032809) in 380 cases and 335 cancer-free controls of non-Hispanic Whites, who were frequency-matched by age (±5 yr), sex, smoking, and drinking status. We found that each individual polymorphism had only a modest impact on risk of SCCHN, particularly in oropharyngeal cancer for rs3810294 and non-oropharyngeal cancer for rs2032809. After we stratified the individuals by HPV16 serology, and used those with the corresponding common homozygous genotype and HPV16 seronegativity as the reference group, for each polymorphism we found that the risk of SCCHN associated with HPV16 seropositivity was higher among those with variant genotypes than those with the corresponding common homozygous genotype. Notably, this effect modification was particularly pronounced in several subgroups including never smokers, never drinkers, younger patients, and patients with oropharyngeal cancer. Furthermore, we also characterized the functional relevance of the two polymorphisms to explore the genotype-phenotype correlation. Our results suggested that the PUMA promoter polymorphisms may be a biomarker for risk of HPV16-associated SCCHN, particularly in never smokers, never drinkers, younger patients, and patients with oropharyngeal cancer. Larger studies are needed to validate our findings.

Duke Scholars

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

October 2012

Volume

51 Suppl 1

Issue

Suppl 1

Start / End Page

E54 / E64

Location

United States

Related Subject Headings

  • Squamous Cell Carcinoma of Head and Neck
  • Risk Factors
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Papillomavirus Infections
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhou, Z., Sturgis, E. M., Liu, Z., Wang, L.-E., Wei, Q., & Li, G. (2012). Genetic variants of a BH3-only pro-apoptotic gene, PUMA, and risk of HPV16-associated squamous cell carcinoma of the head and neck. Mol Carcinog, 51 Suppl 1(Suppl 1), E54–E64. https://doi.org/10.1002/mc.21838
Zhou, Ziyuan, Erich M. Sturgis, Zhensheng Liu, Li-E Wang, Qingyi Wei, and Guojun Li. “Genetic variants of a BH3-only pro-apoptotic gene, PUMA, and risk of HPV16-associated squamous cell carcinoma of the head and neck.Mol Carcinog 51 Suppl 1, no. Suppl 1 (October 2012): E54–64. https://doi.org/10.1002/mc.21838.
Zhou Z, Sturgis EM, Liu Z, Wang L-E, Wei Q, Li G. Genetic variants of a BH3-only pro-apoptotic gene, PUMA, and risk of HPV16-associated squamous cell carcinoma of the head and neck. Mol Carcinog. 2012 Oct;51 Suppl 1(Suppl 1):E54–64.
Zhou, Ziyuan, et al. “Genetic variants of a BH3-only pro-apoptotic gene, PUMA, and risk of HPV16-associated squamous cell carcinoma of the head and neck.Mol Carcinog, vol. 51 Suppl 1, no. Suppl 1, Oct. 2012, pp. E54–64. Pubmed, doi:10.1002/mc.21838.
Zhou Z, Sturgis EM, Liu Z, Wang L-E, Wei Q, Li G. Genetic variants of a BH3-only pro-apoptotic gene, PUMA, and risk of HPV16-associated squamous cell carcinoma of the head and neck. Mol Carcinog. 2012 Oct;51 Suppl 1(Suppl 1):E54–E64.

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

October 2012

Volume

51 Suppl 1

Issue

Suppl 1

Start / End Page

E54 / E64

Location

United States

Related Subject Headings

  • Squamous Cell Carcinoma of Head and Neck
  • Risk Factors
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Papillomavirus Infections
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans