title: Genes involved in DNA repair and nitrosamine metabolism and those located on chromosome 14q32 are dysregulated in nasopharyngeal carcinoma.
abstract: Polymorphisms in nitrosamine metabolism, DNA repair, and immune response genes have been associated with nasopharyngeal carcinoma (NPC). Studies have suggested chromosomal regions involved in NPC. To shed light on NPC etiology, we evaluated host gene expression patterns in 31 NPC and 10 normal nasopharyngeal tissue specimens using the Affymetrix Human Genome U133 Plus 2.0 Array. We focused on genes in five a priori biological pathways and chromosomal locations. Rates of differential expression within these prespecified lists and overall were tested using a bootstrap method. Differential expression was observed for 7.6% of probe sets overall. Elevations in rate of differential expression were observed within the DNA repair (13.7%; P = 0.01) and nitrosamine metabolism (17.5%; P = 0.04) pathways. Differentially expressed probe sets within the DNA repair pathway were consistently overexpressed (93%), with strong effects observed for PRKDC, PCNA, and CHEK1. Differentially expressed probe sets within the nitrosamine metabolism pathway were consistently underexpressed (100%), with strong effects observed for NQ01, CYP2B6, and CYP2E1. No significant evidence of increases in rate of differential expression was seen within the immune/inflammatory pathway. A significant elevation in rate of differential expression was noted for chromosome 4p15.1-4q12 (13.0%; P = 0.04); both overexpression and underexpression were evident (38% and 62%, respectively). An elevation in the rate of differential expression on chromosome 14q32 was observed (11.3%; P = 0.06) with a consistent pattern of gene underexpression (100%; P < 0.0001). These effects were similar when excluding late-stage tumors. Our results suggest that nitrosamine activation and DNA repair are important in NPC. The consistent down-regulation of expression on chromosome 14q32 suggests loss of heterozygosity in this region.
authors.affiliation: National Cancer Institute, 6120 Executive Boulevard, Room 7062, Rockville, MD 20852, USA.
authors.forename: Lori E
authors.initials: LE
authors.lastname: Dodd
authors.forename: Srikumar
authors.initials: S
authors.lastname: Sengupta
authors.forename: I-How
authors.initials: IH
authors.lastname: Chen
authors.forename: Johan A
authors.initials: JA
authors.lastname: den Boon
authors.forename: Yu-Juen
authors.initials: YJ
authors.lastname: Cheng
authors.forename: William
authors.initials: W
authors.lastname: Westra
authors.forename: Michael A
authors.initials: MA
authors.lastname: Newton
authors.forename: Beth F
authors.initials: BF
authors.lastname: Mittl
authors.forename: Lisa
authors.initials: L
authors.lastname: McShane
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Ahlquist
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000379:methods*; D002883:Chromosomes, Human, Pair 14 / Q000648:ultrastructure*; D004260:DNA Repair; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007834:Lasers; D019656:Loss of Heterozygosity; D015233:Models, Statistical; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D009602:Nitrosamines / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D012313:RNA / Q000378:metabolism
chemical_list: D009602:Nitrosamines; D012313:RNA