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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Szkandera, J; Absenger, G; Dandachi, N; Regitnig, P; Lax, S; Stotz, M; Samonigg, H; Renner, W; Gerger, A.
Analysis of functional germline polymorphisms for prediction of response to anthracycline-based neoadjuvant chemotherapy in breast cancer.
Mol Genet Genomics. 2012; 287(9):755-764
Doi: 10.1007/s00438-012-0715-7
Web of Science
PubMed
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- Leading authors Med Uni Graz
- Gerger Armin
- Szkandera Joanna
- Co-authors Med Uni Graz
- Absenger Gudrun
- Dandachi Nadia
- Regitnig Peter
- Renner Wilfried
- Samonigg Hellmut
- Stotz Michael
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- Abstract:
- To elucidate the role of predictive factors on individual's drug response, based on genetic variation, we examined the association between eight germline polymorphisms in genes involved in protection against oxidative stress, apoptosis, oncogenic transformation, proliferation, immune response and DNA repair (TP53, NQO1, IL6, TLR4 and XRCC1) and the pathological response to anthracycline-based neoadjuvant chemotherapy in 70 patients with breast cancer. The DNA was genotyped for eight polymorphisms in five genes (TP53, NQO1, IL6, TLR4 and XRCC1) by 5'-exonuclease (TaqMan™) technology. Fisher's exact test was used to evaluate the association between genotype, clinicopathological parameters and pathological response. A good pathological response, defined as a pathological complete response or residual isolated invasive tumor cells, was found significantly more frequently for estrogen (ER) and progesterone receptor (PR) negative breast carcinomas compared to ER and PR positive and ER or PR positive carcinomas, respectively (43.5 vs. 37.5 and 10.3 %, p = 0.006), and was significantly associated with high tumor grade (G3) (p = 0.002). A non-significant trend towards a good pathological response was shown in patients carrying the Arg/Arg or Arg/Pro TP53 codon 72 gene variant compared to those harboring the Pro/Pro variant (17.6 or 37.9 % vs. 0; p = 0.071). No association was found between NQO1 Pro187Ser, IL6 -174G>C, TLR4 Asp299Gly and Thr399Ile, and XRCC1 Arg194Trp, Arg399Gln and Arg280His and pathological response. The present study shows hormone receptor status and tumor grade as predictors for pathological response to neoadjuvant anthracycline-based chemotherapy. Among various functional germline polymorphisms, a potential predictive value was only found for the TP53 Arg72Pro gene variant.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Anthracyclines - therapeutic use
- Antineoplastic Agents - therapeutic use
- Apoptosis - drug effects
- Breast Neoplasms - drug therapy
- Cell Proliferation - drug effects
- Cell Transformation, Neoplastic - genetics
- DNA Repair - drug effects
- Drug Resistance, Neoplasm - genetics
- Female -
- Humans -
- Middle Aged -
- Neoadjuvant Therapy -
- Oxidative Stress - drug effects
- Polymorphism, Genetic -
- Receptors, Estrogen - analysis
- Receptors, Progesterone - analysis
- Tumor Suppressor Protein p53 - genetics
- Young Adult -
- Find related publications in this database (Keywords)
- Germline polymorphisms
- Anthracycline
- Neoadjuvant chemotherapy
- Breast cancer