Assessment of the Prognostic Value of Two Common Variants of BRCA1 and BRCA2 Genes in Ovarian Cancer Patients Treated with Cisplatin and Paclitaxel: A Gynecologic Oncology Group Study

Abstract

Purpose: BRCA1/BRCA2 germline mutations appear to enhance the platinum-sensitivity, but little is known about the prognostic relevance of polymorphisms in BRCA1/BRCA2 in epithelial ovarian cancer (EOC). This study evaluated whether common variants of BRCA1/BRCA2 are associated with progression-free survival (PFS) and overall survival (OS) in patients with advanced stage sporadic EOC.Experimental Design: The allelic frequency of BRCA1 (2612C > T, P871L-rs799917) and BRCA2 (114A > C, N372H-rs144848) were determined in normal blood DNA from women in Gynecologic Oncology Group protocol #172 phase III trial with optimally resected stage III EOC treated with intraperitoneal or intravenous cisplatin and paclitaxel (C + P). Associations between polymorphisms and PFS or OS were assessed.Results: Two hundred and thirty-two women were included for analyses. African Americans (AA) had different distributions for the two polymorphisms from Caucasians and others. For non-AA patients, the genotype for BRCA1 P871L was distributed as 38% for CC, 49% for CT, and 13% for TT. Median PFS was estimated to be 31, 21, and 21 months, respectively. After adjusting for cell type, residual disease, and chemotherapy regimen, CT/TT genotypes were associated with a 1.40-fold increased risk of disease progression [95% confidence interval (CI) = 1.00–1.95, p = 0.049]. After removing seven patients with known BRCA1 germline mutations, the hazard ratio (HR) was 1.36 (95% CI = 0.97–1.91, p = 0.073). The association between BRCA1 P871L and OS was not significant (HR = 1.25, 95% CI = 0.88–1.76, p = 0.212). Genotype distribution of BRCA2 N372H among non-AA patients was 50, 44, and 6% for AA, AC, and CC, respectively and there is no evidence that this BRCA2 polymorphism was related to PFS or OS.Conclusion: Polymorphisms in BRCA1 P871L or in BRCA2 N372H were not associated with either PFS or OS in women with optimally resected, stage III EOC treated with cisplatin and paclitaxel.

Performance evaluation of the essential dimensions of the primary health care services in six localities of Bogota–Colombia: a cross-sectional study

“…Similar results have also been reported by the studies conducted on the Brazilian Family Health program where a low performance score in family focus, community orientation and accessibility was reported [10,12,26,27]. …”

“…The results of this analysis carried out in six localities in Bogotá confirmed the preliminary results of the pilot assessment in one locality of the city [ 17 ], which found that the lowest rated dimensions were family focus, community orientation, accessibility and financial resources distribution . Similar results have also been reported by the studies conducted on the Brazilian Family Health program where a low performance score in family focus, community orientation and accessibility was reported [ 10 , 12 , 26 , 27 ].…”

Association between BRCA1 rs799917 polymorphism and breast cancer risk: A meta-analysis of 19,878 subjects

“…Though no functional researches have been performed to date, it is credible to say that this amino acid substitution can alter protein function to some degree [21]. Since the discovery of the BRCA1 rs799917 polymorphism, besides breast cancer, it has been widely researched in ovarian cancer [36], cervical cancer [37], non-small cell lung cancer [38], esophageal squamous cell carcinoma [39] and even nonHodgkin lymphoma [40].…”

Screening of BRCA1 variants c.190T>C, 1307delT, g.5331G>A and c.2612C>T in breast cancer patients from North India

“…When assessed for response to therapy, p.Pro871Leu showed no association with either advanced phases of CML or treatment response (Gutierrez-Malacatt et al, 2016). The CT/TT genotypes have been reported to be associated with ovarian cancer progression in non-African American patients, but not with progression-free survival (PFS) and overall survival (OS) in patients treated with cisplatin and paclitaxel (Tian et al, 2013). The TT genotype has been reported to not only contribute to increased breast cancer risk associated with combined estrogen monotherapy in postmenopausal women in Germany (Abbas et al, 2010), but also with recurrence of TNBC after radiotherapy in Han Chinese (Shi et al, 2017).…”