Document Detail

Germ line variation in TP53 regulatory network genes associates with breast cancer survival and treatment outcome.
MedLine Citation:
PMID:  23034890     Owner:  NLM     Status:  Publisher    
Germ line 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 germ line variation in these genes in 925 Finnish breast cancer patients and further analyzed 5 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 4701 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.
Maral Jamshidi; Marjanka K Schmidt; Thilo Dörk; Montserrat Garcia-Closas; Tuomas Heikkinen; Sten Cornelissen; Alexandra J van den Broek; Peter Schürmann; Andreas Meyer; Tjoung-Won Park-Simon; Jonine Figueroa; Mark Sherman; Jolanta Lissowska; Garrett Teoh Hor Keong; Astrid Irwanto; Marko Laakso; Sampsa Hautaniemi; Kristiina Aittomäki; Carl Blomqvist; Jianjun Liu; Heli Nevalinna
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 UICC.
Department of Obstetrics and Gynecology, Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, P.O. Box 700, 00029 Helsinki, Finland.
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