1.
A polymorphism in the base excision repair gene PARP2 is associated with differential prognosis by chemotherapy among postmenopausal breast cancer patients.
Seibold, P, Schmezer, P, Behrens, S, Michailidou, K, Bolla, MK, Wang, Q, Flesch-Janys, D, Nevanlinna, H, Fagerholm, R, Aittomäki, K, et al
BMC cancer. 2015;:978
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.
2.
[Meta-analysis on treatment of non-small cell lung cancer with brucea javanica oil emulsion in combination with platinum-contained first-line chemotherapy].
Wang, Q, Wang, M, He, X, Gao, T, Cao, H, Dou, W, Tian, J
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. 2012;(13):2022-9
Abstract
OBJECTIVE To study the efficacy and safety of brucea javanica oil emulsion (BJOE) combining platinum-contained first-line chemotherapy in treating non small cell lung cancer (NSCLC). METHOD Cochrane library, PubMed, EMBASE, VIP, CBM and CNKI were searched through computers. The search was finished in February, 2011. Randomized controlled trials (RCTs) of BJOE combining platinum-contained first-line chemotherapy were included. Two researchers extracted data and assess literature quality separately,and made a meta-analyses by RevMan 5.1.2 software. RESULT Totally 22 RCTs involving 1512 patients were included. The Meta-analysis showed that compared with the pure application of platinum-contained first-line chemotherapy,the combination of BJOE and chemotherapy can enhance the near-term curative effect (RR = 1. 31, 95% CI: 1.18-1.45, P < 0. 000 01), improve the quality of life (RR = 1.78, 95% CI: 1.51-2. 09, P < 0.00001) and reduce the suppression of bone marrow (OR = 0.37, 95% CI: 0. 27-0. 51, P < 0.00001) and the gastrointestinal reactions (OR = 0.59, 95% CI: 0.44-0.80, P = 0.0007) ,with an improvement in organism immunity. CONCLUSION The current evidence indicates that BJOE can enhance the chemotherapeutic effect on NSCLC patients, improve the quality of life and reduce adverse effect of platinum-contained chemotherapeutics and thus it is worth referring in clinic.