ERCC1, XPD and RAI mRNA levels in lymphocytes are not associated with lung cancer risk in a prospective study of Danes |
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| Authors: | Vogel Ulla Nexø Bjørn A Tjønneland Anne Wallin Håkan Hertel Ole Raaschou-Nielsen Ole |
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| Institution: | 1. Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo;2. Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki;3. Department of Gastrointestinal Medical Oncology, Shikoku Cancer Center, Matsuyama;4. Department of Gastroenterology, Saitama Cancer Center, Kita-adachi;5. Department of Gastroenterology, Chiba Cancer Center, Chiba;6. Department of Clinical Oncology, Kobe City Medical Center General Hospital, Kobe;7. Department of Gastroenterology, Keio University, School of Medicine, Tokyo;8. Department of Gastroenterology, Showa University, School of Medicine, Tokyo;9. Department of Clinical Oncology, Tonan Hospital, Sapporo;10. Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Kasama;11. Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama;12. Department of Gastroenterology, Yokohama Municipal Citizen''s Hospital, Yokohama;13. Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi;14. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya;15. JCOG Data Center/Operations Office, National Cancer Center, Tokyo;16. National Cancer Center, Exploratory Oncology Research and Clinical Trial Center, Kashiwa, Japan |
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| 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. |
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