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A polymorphism in the base excision repair gene PARP2 is associated with differential prognosis by chemotherapy among postmenopausal breast cancer patients

Overview of attention for article published in BMC Cancer, December 2015
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Title
A polymorphism in the base excision repair gene PARP2 is associated with differential prognosis by chemotherapy among postmenopausal breast cancer patients
Published in
BMC Cancer, December 2015
DOI 10.1186/s12885-015-1957-7
Pubmed ID
Authors

Petra Seibold, Peter Schmezer, Sabine Behrens, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Dieter Flesch-Janys, Heli Nevanlinna, Rainer Fagerholm, Kristiina Aittomäki, Carl Blomqvist, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M. Hartikainen, Diether Lambrechts, Hans Wildiers, Vessela Kristensen, Grethe Grenaker Alnæs, Silje Nord, Anne-Lise Borresen-Dale, Maartje J. Hooning, Antoinette Hollestelle, Agnes Jager, Caroline Seynaeve, Jingmei Li, Jianjun Liu, Keith Humphreys, Alison M. Dunning, Valerie Rhenius, Mitul Shah, Maria Kabisch, Diana Torres, Hans-Ulrich Ulmer, Ute Hamann, Joellen M. Schildkraut, Kristen S. Purrington, Fergus J. Couch, Per Hall, Paul Pharoah, Doug F. Easton, Marjanka K. Schmidt, Jenny Chang-Claude, Odilia Popanda

Abstract

Personalized therapy considering clinical and genetic patient characteristics will further improve breast cancer survival. Two widely used treatments, chemotherapy and radiotherapy, can induce oxidative DNA damage and, if not repaired, cell death. Since base excision repair (BER) activity is specific for oxidative DNA damage, we hypothesized that germline genetic variation in this pathway will affect breast cancer-specific survival depending on treatment. We assessed in 1,408 postmenopausal breast cancer patients from the German MARIE study whether cancer specific survival after adjuvant chemotherapy, anthracycline chemotherapy, and radiotherapy is modulated by 127 Single Nucleotide Polymorphisms (SNPs) in 21 BER genes. For SNPs with interaction terms showing p < 0.1 (likelihood ratio test) using multivariable Cox proportional hazard analyses, replication in 6,392 patients from nine studies of the Breast Cancer Association Consortium (BCAC) was performed. rs878156 in PARP2 showed a differential effect by chemotherapy (p = 0.093) and was replicated in BCAC studies (p = 0.009; combined analysis p = 0.002). Compared to non-carriers, carriers of the variant G allele (minor allele frequency = 0.07) showed better survival after chemotherapy (combined allelic hazard ratio (HR) = 0.75, 95 % 0.53-1.07) and poorer survival when not treated with chemotherapy (HR = 1.42, 95 % 1.08-1.85). A similar effect modification by rs878156 was observed for anthracycline-based chemotherapy in both MARIE and BCAC, with improved survival in carriers (combined allelic HR = 0.73, 95 % CI 0.40-1.32). None of the SNPs showed significant differential effects by radiotherapy. Our data suggest for the first time that a SNP in PARP2, rs878156, may together with other genetic variants modulate cancer specific survival in breast cancer patients depending on chemotherapy. These germline SNPs could contribute towards the design of predictive tests for breast cancer patients.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Finland 1 2%
Unknown 55 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 14%
Professor 6 11%
Researcher 5 9%
Librarian 4 7%
Student > Master 4 7%
Other 12 21%
Unknown 17 30%
Readers by discipline Count As %
Medicine and Dentistry 16 29%
Biochemistry, Genetics and Molecular Biology 7 13%
Pharmacology, Toxicology and Pharmaceutical Science 3 5%
Agricultural and Biological Sciences 2 4%
Nursing and Health Professions 2 4%
Other 8 14%
Unknown 18 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 September 2016.
All research outputs
#15,351,847
of 22,835,198 outputs
Outputs from BMC Cancer
#4,113
of 8,307 outputs
Outputs of similar age
#228,893
of 390,452 outputs
Outputs of similar age from BMC Cancer
#84
of 187 outputs
Altmetric has tracked 22,835,198 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,307 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 390,452 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 187 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.