title: Genetic polymorphisms of the human  cytomegalovirus UL144 gene in colorectal cancer  and its association with clinical outcome.
abstract: Human cytomegalovirus (HCMV) has been increasingly detected in colorectal cancer (CRC), and genetic polymorphisms in HCMV affect its pathogenesis. This study aimed to investigate HCMV genetic polymorphisms in CRC and its correlation with the clinical outcomes. We performed PCR and sequencing of a viral immunomodulatory gene, UL144, in clinical isolates and CRC specimens. The nucleotide and amino acid sequences were aligned, and a phylogenetic tree was constructed. The clinical, pathological and survival data were compared among tumours with different UL144 genotypes. HCMV was detected in 49 (47.8 %) of the tumour specimens. Genotype A predominated in 43 samples (22/43; 51.2 %) with successful sequencing, followed by genotype B (13/43; 30.2 %) and genotype C (8/43; 18.6 %). The genotypic distribution was similar to that of the clinical isolates and those reported in other Asian populations. The amino acid sequence of genotype B was the most conserved. For stage II and III CRC patients with HCMV-positive tumours, disease-free survival (DFS) varied among the three major genotypes (P50.0046). The presence of genotype B virus in the tumours was associated with a shorter DFS and independently predicted tumour recurrence in a multivariate Cox proportional hazards model (hazard ratio, 5.79; 95 % confidence interval, 1.30–25.81; P50.021). By reverse transcription PCR, tumour samples with genotype B viruses had the highest rate of UL144 expression. Our results suggest that genetic polymorphisms of HCMV UL144 are associated with clinical outcome in CRC and that HCMV may play an immunomodulatory role in the tumour microenvironment of CRC.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsin-Pai
authors.initials: HP
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Jeng-Kai
authors.initials: JK
authors.lastname: Jiang
authors.affiliation: Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Chan
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wan-Huai
authors.initials: WH
authors.lastname: Teo
authors.affiliation: Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Chih-Yung
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Department of Pathology, National Yang-Ming University Hospital, Yilan, Taiwan.
authors.forename: Yen-Chung
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
authors.affiliation: Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Microbiology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yu-Jiun
authors.initials: YJ
authors.lastname: Chan
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000401:mortality / Q000821:virology*; D003587:Cytomegalovirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D008562:Membrane Glycoproteins; C119624:UL144 ORF protein, Human herpesvirus 5; D014764:Viral Proteins