| Literature DB >> 29379198 |
Jiang Chang1, Rong Zhong1, Jianbo Tian1, Jiaoyuan Li1, Kan Zhai2,3, Juntao Ke1, Jiao Lou1, Wei Chen1, Beibei Zhu1, Na Shen1, Yi Zhang1, Ying Zhu1, Yajie Gong1, Yang Yang1, Danyi Zou1, Xiating Peng1, Zhi Zhang4, Xuemei Zhang5, Kun Huang6, Tangchun Wu7, Chen Wu8, Xiaoping Miao9, Dongxin Lin2.
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.Entities:
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Year: 2018 PMID： 29379198 DOI： 10.1038/s41588-018-0045-8
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330