Abstract 3162
Background
The prevalence of BRCA1 and BRCA2 mutations varies among individual racial and ethnic groups. While, molecular epidemiological data on Chinese ovarian cancer patients is still insufficient.
Methods
Here, we performed a multicenter study to investigate the clinical and molecular characteristics of 1,059 ovarian cancer patients. A hereditary cancer multigene panel including all NCCN recommended homologues recombination repair genes was performed.
Results
Totally, 1,059 patients with ovarian (n = 982, 92.7%), fallopian tube (n = 63, 5.9%) and peritoneal (n = 14, 1.3%) cancer were recruited from 18 medical centers in China. 314 of 1,059 patients carried deleterious germline aberration in HRR genes including BRCA1 (19.1%), BRCA2 (6.5%) and other HRR genes (4.1%). Another 15 patients carried abnormality in MMR pathway as well as genes of other familial cancer syndrome like MUTYH, STK11, TP53. Histologically, BRCA1/2 mutations, in our study, were enriched not only in HGSC, but also in HGSC (P < 0.001 for BRCA1, P = 0.05 for BRCA2), which was seldomly investigated. Patients with germline BRCA1 mutations associated with early-onset (age≤50 years, P < 0.001), higher chances of breast cancer (P < 0.001), family history of HBOC (P < 0.001) and relapse after initial treatment (P = 0.068). Recurrent patients harbored more deleterious mutations than primary patients although the differences reached no significance in patients with HGSC subtype (P = 0.056), suggesting a selection bias. Moreover, it is of our greatest interest that sensitivity to platinum-based therapy was largely depending on BRCA2 status (P = 0.023 for all ovarian cancer, P = 0.035 for HGSC). While, no significant association was found in BRCA1 mutated group (P = 0.3).
Conclusions
To date, it is the largest study on predisposition genes in ovarian carcinoma in Chinese population. Our study disclosed a more complexed spectrum as well as higher rate of germline aberrations compared with previously published data. Etiologically, our data revealed a putative contribution of mutated BRCA1 gene to the onset of ovarian cancer with serous phenotype. Clinically, BRCA2 and other HRR and MMR genes may be used as useful predictive tools for Platinum sensitivity.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
BGI Genomics.
Funding
BGI genomics.
Disclosure
C. Zhu: Full / Part-time employment: BGI genomics. D. Shao: Full / Part-time employment: BGI genomics. All other authors have declared no conflicts of interest.
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