title: ERCC1, XPD and RAI mRNA levels in lymphocytes are not associated with lung cancer risk in a prospective study of Danes.
abstract: Low DNA-repair capacity has been associated with increased risk of several types of cancer. mRNA levels of the nucleotide excision repair genes ERCC1 and XPD have been shown to correlate with the DNA-repair capacity. Likewise, mRNA levels of several DNA-repair genes including ERCC1 have been shown to be lower in lymphocytes from patients with lung cancer and head and neck cancer compared with healthy persons. In these studies, the low DNA-repair gene expression levels could be either a risk factor for disease or a consequence of the same. In this nested case-cohort study, which to our knowledge, is the first prospective study of DNA-repair gene mRNA levels as predictors of lung cancer, we have investigated the occurrence of lung cancer in relation to the mRNA level of the two DNA-repair genes ERCC1 and XPD and the NF kappaB inhibitor RAI in blood samples prior to disease. Among 54,220 members of a Danish prospective cohort study, 265 lung cancer cases were identified and a sub-cohort comprising 272 individuals was used for comparison. The expression levels of the three adjacent genes were found to be highly inter-correlated, to be higher in women compared to men and to be lower in older individuals. The incidence rate ratios for lung cancer in association with one log-unit increase (natural logarithm) in mRNA levels were 1.12 (CI=0.89-1.41) for ERCC1, 1.00 (CI=0.83-1.21) for XPD and 1.25 (0.89-1.74) for RAI. In conclusion, this study indicated no association between mRNA expression of the DNA-repair genes ERCC1 and XPD and risk of subsequent development of lung cancer.
authors.affiliation: National Institute of Occupational Health, Lersø Parkallé 105, DK-2100 Copenhagen, Denmark. ubv@ami.dk
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Ole
authors.initials: O
authors.lastname: Hertel
authors.forename: Ole
authors.initials: O
authors.lastname: Raaschou-Nielsen
mesh_terms: D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics*; D003718:Denmark; D004720:Endonucleases / Q000097:blood / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D051759:Xeroderma Pigmentosum Group D Protein / Q000097:blood / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human