title: A novel variant on chromosome 6p21.1 is associated with the risk of developing colorectal cancer: a two-stage case-control study in Han Chinese.
abstract: Genes in inflammatory pathways play a pivotal role in the development of colorectal cancer. We conducted a two-stage case-control study and aimed at screening the colorectal cancer-associated genetic variations in inflammatory genes.
  
  
  
  Twenty-three candidate variants were genotyped in 952 primary colorectal cancer cases and 875 cancer-free controls from eastern China. Promising single nucleotide polymorphisms were further genotyped in 518 cases and 554 controls from middle China. Expression quantitative trait loci and differential gene expression analyses were performed for the associated gene.
  
  
  
  rs2282151 presented consistently significant associations with the risk of colorectal cancer in both stages (odds ratio (95 % confidence interval) = 1.30 (1.16-1.46), risk allele = C, Pcombined= 8.9E-6). Gene expression quantitative trait loci analyzes uncovered consistent cis-regulatory signals which showed that the C allele of rs2282151 was associated with increased expression level of heat shock protein 90 alpha family class B member 1 (HSP90AB1). Then we found that the mRNA expression levels of HSP90AB1 were significantly higher in tumor tissues than normal tissues (fold-change = 1.83) in 28 pairs of colorectal tissue samples. The expression difference was consistent with data from online datasets. Additionally, we observed notable peaks of H3K27ac and H3K4me3 near the first intron of HSP90AB1 using ChIP-seq data from multiple cell lines (including HCT116).
  
  
  
  Our findings indicate that the C allele of the novel colorectal cancer-associated variant rs2282151 is associated with increased expression levels of HSP90AB1, which is expressed higher in colorectal tumor tissues than in normal tissues.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang Province, China.|Department of Chronic Non-Communicable Diseases Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province and Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang Province, China.
authors.forename: Feixia
authors.initials: F
authors.lastname: Pan
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province and Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Human Tissue Bank, Taizhou Hospital of Zhejiang Province, Zhejiang, China.|Medical Research Center, Taizhou Hospital of Zhejiang Province, Zhejiang, China.
authors.forename: Aifen
authors.initials: A
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang Province, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang Province, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Lv
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province and Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Computer Science and Technology, College of Engineering, Lishui University, Lishui, Zhejiang, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang Province, China. zhuym@zju.edu.cn.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China. lmp@zju.edu.cn.|Key Laboratory of Disease Proteomics of Zhejiang Province and Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, China. lmp@zju.edu.cn.
authors.forename: Maode
authors.initials: M
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human
keywords: Colorectal cancer; Genetic variant; HSP90; Inflammation