1. Exome-wide analyses identify low-frequency variant in CYP26B1 and additional coding variants associated with esophageal squamous cell carcinoma
- Author
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Kun Huang, Zhi Zhang, Yi Zhang, Jiaoyuan Li, Beibei Zhu, Yang Yang, Yajie Gong, Rong Zhong, Ying Zhu, Juntao Ke, Xiating Peng, Chen Wu, Wei Chen, Kan Zhai, Xuemei Zhang, Danyi Zou, Jianbo Tian, Dongxin Lin, Na Shen, Xiaoping Miao, Tangchun Wu, Jiao Lou, and Jiang Chang
- Subjects
0301 basic medicine ,Case-control study ,Retinoic acid ,Genome-wide association study ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Polymorphism (computer science) ,Genotype ,Genetics ,Cancer research ,Exome ,Allele frequency ,Genetic association - Abstract
Genome-wide association studies have identified common variants associated with risk of esophageal squamous cell carcinoma (ESCC). However, these common variants cannot explain all heritability of ESCC. Here we report an exome-wide interrogation of 3,714 individuals with ESCC and 3,880 controls for low-frequency susceptibility loci, with two independent replication samples comprising 7,002 cases and 8,757 controls. We found six new susceptibility loci in CCHCR1, TCN2, TNXB, LTA, CYP26B1 and FASN (P = 7.77 × 10−24 to P = 1.49 × 10−11), and three low-frequency variants had relatively high effect size (odds ratio > 1.5). Individuals with the rs138478634-GA genotype had significantly lower levels of serum all-trans retinoic acid, an anticancer nutrient, than those with the rs138478634-GG genotype (P = 0.0004), most likely due to an enhanced capacity of variant CYP26B1 to catabolize this agent. These findings emphasize the important role of rare coding variants in the development of ESCC. Exome-wide analyses identify low-frequency coding variants associated with esophageal squamous cell carcinoma. One of the risk variants, in CYP26B1, is associated with enhanced enzymatic activity and lower levels of all-trans retinoic acid in serum.
- Published
- 2018