Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3).
- Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA.
- Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
- Behavior and Epidemiology Research Group, American Cancer Society, Inc., Atlanta, GA.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD.
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
- Department of Health Promotion Science, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ.
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN.
- Department of Obstetrics and Gynecology, Population Health, Environmental Medicine and Perlmutter Cancer Center, New York University School of Medicine, New York, NY.
- Department of Population Health and Environmental Medicine and Perlmutter Cancer Centre, New York University School of Medicine, New York, NY.
- Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
- Department of Prevention, Keck School of Medicine, University of Southern California, Los Angeles, CA.
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN.
- Cancer Epidemiology and Division, Cancer Council Victoria, Melbourne, VIC, Australia.
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
- Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
- HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway.
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health & Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
- State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
- Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
- George W. Comstock Center for Public Health Research and Prevention Health Monitoring Unit, Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
- Department of Clinical Science, University of Bergen, Bergen, Norway.
- Bevital AS, Bergen, Norway.
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA.
- Department of Surgery, Skåne University Hospital Malmö Lund University, Malmö, Sweden.
- MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
- Health Services and Systems Research, Duke-NUS Medical School, Singapore.
Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
- 2007-0004: A Whole Genome Association Study (WGAS) of Lung Cancer and Smoking (Neil Caporaso - 2007)