A polymorphism in the base excision repair gene PARP2 is associated with differential prognosis by chemotherapy among postmenopausal breast cancer patients
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Fecha
2015-12-16Autor(es)
Seibold, PetraSchmezer, Peter
Behrens, Sabine
Michailidou, Kyriaki
Bolla, Manjeet K.
Wang, Qin
Flesch Janys, Dieter
Nevanlinna, Heli
Fagerholm, Rainer
Aittomaki, Kristiina
Blomqvist, Carl
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli Matti
Hartikainen, Jaana M.
Lambrechts, Diether
Wildiers, Hans
Kristensen, Vessela
Alnaes, Grethe Grenaker
Nord, Silje
Borresen Dale, Anne Lise
Hooning, Maartje J.
Hollestelle, Antoinette
Jager, Agnes
Seynaeve, Caroline
Li, Jingmei
Liu, Jianjun
Humphreys, Keith
Dunning, Alison M.
Rhenius, Valerie
Shah, Mitul
Kabisch, Maria
Torres, Diana
Ulmer, Hans Ulrich
Hamann, Ute
Schildkraut, Joellen M.
Purrington, Kristen S.
Couch, Fergus J.
Hall, Per
Pharoah, Paul
Easton, Doug F.
Schmidt, Marjanka K.
Chang-Claude, Jenny
Popanda, Odilia
Autor(es) Corporativo(s)
Pontificia Universidad Javeriana. Facultad de Medicina. Instituto de Genética Humana
Tipo
Artículo de revista
ISSN
1471-2407 (Electrónico)
Páginas
1-11
Tipo de artículo
Artículo de investigación
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Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Enlace al recurso
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1957-7Fuente
BMC Cancer; Vol. 15 Núm. 978 (2015)
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