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Poster display session

5194 - CASP9 c.-1339A>G and CASP3 c.-1191A>G polymorphisms in susceptibility and outcome of head and neck squamous cell carcinoma

Date

10 Sep 2017

Session

Poster display session

Presenters

Ericka Costa

Citation

Annals of Oncology (2017) 28 (suppl_5): v372-v394. 10.1093/annonc/mdx374

Authors

E.F.D. Costa1, L. Lopes-Aguiar1, G.A.S. Nogueira1, T.R.P. Lima1, V.T. Liutti1, F. Leal1, V.C.A. Santos1, J.A. Rinck-Junior1, G.J. Lourenço1, C.S.P. Lima2

Author affiliations

  • 1 Department Of Internal Medicine, University of Campinas, 13083-970 - Campinas/BR
  • 2 Department Of Internal Medicine, University of Campinas, 13083-888 - Campinas/BR
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Resources

Abstract 5194

Background

We analyzed herein the roles of CASP9 c.-1339A>G (rs4645978) and CASP3 c.-1191A>G (rs12108497) single nucleotide polymorphisms (SNPs) of intrinsic apoptosis pathway on risk and behavior of head and neck squamous cell carcinoma (HNSCC).

Methods

DNA of 350 HNSCC patients and 350 controls was analyzed by polymerase chain reaction method and enzymatic digestion for genotyping. Patients were treated according to the Institutional protocol, including surgery, radio and chemotherapy. The statistical analyses were realized using chi-square, logistic regression model, multifactor dimensionality reduction (MDR), Kaplan-Meier, and univariate and multivariate Cox analyses.

Results

CASP3 c.-1191AG or GG genotype was more common in patients with overall HNSCC (63.4% versus 53.4%, P= 0.013), male patients with overall HNSCC (65.5% versus 53.4%, P= 0.011), patients with SCC of oral cavity (OCSCC) (68.0% versus 53.4%, P= 0.02) and SCC of pharynx (PSCC) (62.7% versus 53.4%, P =  0.010) than in controls; carriers of genotypes were under 2.15 and 2.34-fold increased risks of overall HNSCC, 2.75 and 2.67-fold increased risks of OCSCC and PSCC, respectively. Interactions of CASP9 and CASP3 SNPs and tobacco on HNSCC, OCSCC, PSCC, and laryngeal SCC risks were evident in study (P< 0.01). At 60 months of follow-up, event-free survival was worst in patients with CASP9 c.-1339GG genotype (35.9% versus 45.1%, P =  0.04) compared to others (Kaplan-Meier estimates). Patients with CASP9 c.-1339GG genotype and CASP9 c.-1339GG plus CASP3 c.-1191GG genotypes had 1.46 more chances of disease progression or relapse and 2.66 more chances of evolving to death in univariate and multivariate analyses, respectively.

Conclusions

We present, for the first time, preliminary evidence that inherited abnormalities in the intrinsic apoptosis pathway, related to CASP9 c.-1339A>G and CASP3 c.-1191A>G SNPs, are important determinants of HNSCC risk and outcome. Financial support: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

Clinical trial identification

Legal entity responsible for the study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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