BRCA1 missense polymorphisms are associated with poor prognosis of pancreatic cancer patients in a Chinese population
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Ying Zhu1,*, Kan Zhai2,*, Juntao Ke1, Jiaoyuan Li1, Yajie Gong1, Yang Yang1, Jianbo Tian1, Yi Zhang1, Danyi Zou1, Xiating Peng1, Jing Gong1, Rong Zhong1, Kun Huang3, Jiang Chang1, Xiaoping Miao1
1Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
3Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China
*These authors contribute equally to this work
Jiang Chang, email: [email protected]
Xiaoping Miao, email: [email protected]
Keywords: prognosis, pancreatic cancer, BRCA, SNP
Received: February 09, 2017 Accepted: March 15, 2017 Published: March 21, 2017
Pancreatic cancer is a highly lethal disease with limited prognostic marker. BRAC1 and BRCA2 are two classic tumor suppressor genes which play an important role in DNA repair. Somatic mutations and germline genetic variants on BRCA1/2 have been found associated with the tumorigenesis of pancreatic cancer. However, the correlations between BRCA1/2 polymorphism and pancreatic cancer prognosis remained unknown. In this study, we genotyped three tag missense variants on BRCA1/2 in 603 sporadic pancreatic cancer patients in a Chinese population. We found rs1799966 on BRCA1 was associated with poor prognosis of pancreatic cancer patients with hazard ratio being 1.23 (95% CI: 1.09–1.40, P = 0.0010). Further stratification analyses showed that significant correlation was particularly in locally advanced stage patients with hazard ratio being 1.36 (95% CI: 1.13–1.64, P = 0.0014), but not in patients in local stage (P = 0.1139) or metastatic stage (P = 0.5185). Two missense variants (rs766173 and rs144848) on BRAC2 showed no significant correlation with pancreatic cancer patients’ overall survival. In conclusion, we identified a germline missense variant on BRAC1 significantly associated with poor prognosis of pancreatic cancer patients with locally advanced stage. These results may contribute to the precision medicine of this disease.
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