Germ line variation in TP53 regulatory network genes associates with breast cancer survival and treatment outcome
| Autor: | Tjoung Won Park-Simon, Astrid Irwanto, Heli Nevanlinna, Jolanta Lissowska, Jianjun Liu, Maral Jamshidi, Andreas Meyer, Peter Schürmann, Garrett Teoh Hor Keong, Alexandra J. van den Broek, Carl Blomqvist, Tuomas Heikkinen, Sampsa Hautaniemi, Sten Cornelissen, Montserrat Garcia-Closas, Thilo Dörk, Jonine D. Figueroa, Marko Laakso, Marjanka K. Schmidt, Kristiina Aittomäki, Mark E. Sherman |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Oncology
Cancer Research AMP-Activated Protein Kinases 0302 clinical medicine Genotype Gene Regulatory Networks Protein Phosphatase 2 RNA Neoplasm Neoplasm Metastasis 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Carcinoma Ductal Breast Proto-Oncogene Proteins c-mdm2 Middle Aged Prognosis 3. Good health Survival Rate 030220 oncology & carcinogenesis Hormonal therapy Female Adult medicine.medical_specialty Antineoplastic Agents Hormonal Single-nucleotide polymorphism Breast Neoplasms Nerve Tissue Proteins Biology Real-Time Polymerase Chain Reaction Polymorphism Single Nucleotide Article 03 medical and health sciences Breast cancer Germline mutation Internal medicine medicine Adjuvant therapy Humans Neoplasm Invasiveness RNA Messenger Allele Survival rate Germ-Line Mutation 030304 developmental biology medicine.disease Carcinoma Lobular Cancer research Neoplasm Grading Tumor Suppressor Protein p53 |
| Zdroj: | International Journal of Cancer; Vol 132 |
| Popis: | Germline variation in the TP53 network genes PRKAG2, PPP2R2B, CCNG1, PIAS1 and YWHAQ was previously suggested to have an impact on drug response in vitro. Here, we investigated the effect on breast cancer survival of germline variation in these genes in 925 Finnish breast cancer patients and further analyzed five single nucleotide polymorphisms (SNPs) in PRKAG2 (rs1029946, rs4726050, rs6464153, rs7789699) and PPP2R2B (rs10477313) for 10-year survival in breast cancer patients, interaction with TP53 R72P and MDM2-SNP309, outcome after specific adjuvant therapy and correlation to tumor characteristics in 4,701 invasive cases from four data sets. We found evidence for carriers of PRKAG2-rs1029946 and PRKAG2-rs4726050 having improved survival in the pooled data (HR 0.53, 95% CI 0.3–0.9; p = 0.023 for homozygous carriers of the rare G-allele and HR 0.85, 95% CI 0.7–0.9; p = 0.049 for carriers of the rare G allele, respectively). PRKAG2-rs4726050 showed a significant interaction with MDM2-SNP309, with PRKAG2-rs4726050 rare G-allele having a dose-dependent effect for better breast cancer survival confined only to MDM2 SNP309 rare G-allele carriers (HR 0.45, 95% CI 0.2–0.7; p = 0.001). This interaction also emerged as an independent predictor of better survival (p = 0.047). PPP2R2B-rs10477313 rare A-allele was found to predict better survival (HR 0.82, 95% CI 0.6–0.9; p = 0.018), especially after hormonal therapy (HR 0.66, 95% CI 0.5–0.9; p = 0.048). These findings warrant further studies and suggest that genetic markers in TP53 network genes such as PRKAG2 and PPP2R2B might affect prognosis and treatment outcome in breast cancer patients. |
| Databáze: | OpenAIRE |
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