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PI3K/PTEN/AKT/mTOR polymorphisms: Association with clinical outcome in patients with head and neck squamous cell carcinoma receiving cetuximab‐docetaxel
Author(s) -
Pfisterer Katharina,
Fusi Alberto,
Klinghammer Konrad,
Knödler Maren,
nenmacher Anika,
Keilholz Ulrich
Publication year - 2015
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.23604
Subject(s) - head and neck squamous cell carcinoma , pten , cetuximab , medicine , oncology , single nucleotide polymorphism , hazard ratio , docetaxel , population , genotype , head and neck cancer , confidence interval , cancer , pi3k/akt/mtor pathway , biology , apoptosis , gene , colorectal cancer , genetics , environmental health
Background The purpose of this study was to determine whether single nucleotide polymorphisms (SNPs) in AKT1 , AKT2 , FRAP1 , PIK3CA , and PTEN were associated with treatment response and clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC). Methods Genomic DNA was extracted from formalin‐fixed tissue of 45 patients with recurrent or initially metastatic HNSCC, and SNPs were genotyped by means of real‐time polymerase chain reaction (PCR) system or direct sequencing. Results The AKT2:rs8100018 and the PTEN:rs12569998 homozygous variants resulted as associated with an increased risk of progression (hazard ratio [HR], 4.83; 95% confidence interval [CI], 1.11–21.03; and HR, 2.36; 95% CI, 1.24–4.50, respectively). An additive effect on risk of progression was observed. The AKT2:rs8100018 homozygous variant was significantly associated with a higher risk of death (HR, 3.57; 95% CI, 1.06–12.00), whereas the presence of at least one variant allele of AKT1:rs3803304 was associated with a lower risk of death (HR, 0.51; 95% CI, 0.27–0.97). Conclusion We identified combined genotypes associated with outcome of HNSCC, which might have an impact for identification of a target population for cetuximab‐docetaxel treatment. Results should be considered as an initial finding and warrant validation in larger clinical trials. © 2014 Wiley Periodicals, Inc. Head Neck 37 : 471–478, 2015