BRCA1 missense polymorphisms are associated with poor prognosis of pancreatic cancer patients in a Chinese population

Abstract

// Ying Zhu 1, * , Kan Zhai 2, * , Juntao Ke 1 , Jiaoyuan Li 1 , Yajie Gong 1 , Yang Yang 1 , Jianbo Tian 1 , Yi Zhang 1 , Danyi Zou 1 , Xiating Peng 1 , Jing Gong 1 , Rong Zhong 1 , Kun Huang 3 , Jiang Chang 1 , Xiaoping Miao 1 1 Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China 3 Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, China * These authors contribute equally to this work Correspondence to: Jiang Chang, email: changjiang815@hust.edu.cn Xiaoping Miao, email: Miaoxp@hust.edu.cn Keywords: prognosis, pancreatic cancer, BRCA, SNP Received: February 09, 2017      Accepted: March 15, 2017      Published: March 21, 2017 ABSTRACT 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.