A functional single nucleotide polymorphism of SET8 is prognostic for breast cancer

// Ben Liu 1, * , Xining Zhang 1, * , Fengju Song 1 , Qun Liu 1, 2 , Hongji Dai 1 , Hong Zheng 1 , Ping Cui 1 , Lina Zhang 1 , Wei Zhang 3, 4 , Kexin Chen 1 1 Department of Epidemiology and Biostatistics, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 2 Departments of Neurosurgery, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China 3 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 4 Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA * These authors contributed equally to this work Correspondence to: Kexin Chen, email: chenkexin@tjmuch.com Wei Zhang, email: wzhang@mdanderson.org , wezhang@wakehealth.edu Keywords: SET8, single nucleotide polymorphisms (SNP), rs16917496, prognosis, breast cancer Received: November 30, 2015      Accepted: April 10, 2016      Published: April 29, 2016 ABSTRACT A single-nucleotide polymorphism (SNP) locus rs16917496 (T > C) within the 3′-untranslated region (3′-UTR) of SET8 was associated with susceptibility in several malignancies including breast cancer. To further elucidate the prognostic relevance of this SNP in breast cancer, we conducted a clinical study as well as SET8 expression analysis in a cohort of 1,190 breast cancer patients. We demonstrated the expression levels of SET8 in TT genotype were higher than in CC genotypes, and high levels of SET8 were associated with poor survival. SET8 expression was significantly higher in breast tumor tissue than in paired adjacent normal tissue. In addition, survival analysis in 315 patients showed SNP rs16917496 was an independent prognostic factor of breast cancer outcome with TT genotype associated with poor survival compared with CC/CT genotypes. Thus, this SNP may serve as a genetic prognostic factor and a treatment target for breast cancer. Future studies are warranted.