Genome-wide association study identifies four SNPs associated with response to platinum-based neoadjuvant chemotherapy for cervical cancer

• Published in: Scientific reports Vol. 7; no. 1; p. 41103
• Main Authors: Li, Xiong, Huang, Kecheng, Zhang, Qinghua, Zhou, Jin, Sun, Haiying, Tang, Fangxu, Zhou, Hang, Hu, Ting, Wang, Shaoshuai, Jia, Yao, Yang, Ru, Chen, Yile, Cheng, Xiaodong, Lv, Weiguo, Wu, Li, Xing, Hui, Wang, Lin, Zhou, Shasha, Yao, Yuan, Wang, Xiaoli, Suolang, Quzhen, Shen, Jian, Xi, Ling, Hu, Junbo, Wang, Hui, Chen, Gang, Gao, Qinglei, Xie, Xing, Wang, Shixuan, Li, Shuang, Ma, Ding
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.01.2017; Nature Publishing Group
• Subjects: 45/43; 692/4028/67/1517; 692/53/2423; Adult; Aged; Alleles; Antineoplastic Agents - administration & dosage; Asian Continental Ancestry Group; Biopsy; Cervical cancer; Cervix; Chemotherapy; Drug Therapy - methods; Etiology; Female; Genome-wide association studies; Genome-Wide Association Study; Genomes; Humanities and Social Sciences; Humans; Middle Aged; multidisciplinary; Platinum; Platinum - administration & dosage; Polymorphism, Single Nucleotide; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Survival; Survival Analysis; Treatment Outcome; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - pathology; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep41103

To identify genomic markers associated with the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. A total of 596 patients with stage IA2-IIIB cervical cancer were enrolled in this study. One single nucleotide polymorphism (SNP) (rs6812281, per allele OR = 2.37, P  = 9.0 × 10 −9 ) located at 4q34.3 reached GWAS significance ( P  < 5.0 × 10 −8 ). Another three SNPs, rs4590782 (10q26.2, P  = 1.59 × 10 −5 , per allele OR = 0.48), rs1742101 (14q32.11, P  = 7.11 × 10 −6 , per allele OR = 0.52), and rs1364121 (16q23.3, P  = 3.15 × 10 −6 , per allele OR = 1.98), exhibited strong evidence of associations with response to neoadjuvant chemotherapy. Patients with a C allele (CT + CC) of rs4590782 had better 5-year overall survival rates (82.9% vs. 75.8%, P  = 0.083) and 5-year disease-free survival rate (80.8% vs. 72.7%, P  = 0.021) than those without a C allele. Our findings help to characterize the genetic etiology of the response to neoadjuvant chemotherapy in patients with cervical cancer.