Xīn Gào1, Hermann Brenner2, Bernd Holleczek3, Katarina Cuk4, Yan Zhang4, Ankita Anusruti1, Yang Xuan1, Yiwei Xu5, Ben Schöttker6. 1. Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany; Network Aging Research, Heidelberg University, Germany. 2. Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. 3. Saarland Cancer Registry, Saarland, Germany. 4. Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany. 5. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 6. Division of Clinical Epidemiology and Ageing Research, German Cancer Research Center, Heidelberg, Germany; Network Aging Research, Heidelberg University, Germany; Institute of Health Care and Social Sciences, FOM University, Essen, Germany. Electronic address: b.schoettker@dkfz.de.
Abstract
BACKGROUND: Urinary 8-isoprostane is an established biomarker for lipid peroxidation. However, the association between its pre-diagnostic levels and cancer incidence has rarely been evaluated. METHODS: 8793 older adults from the German ESTHER cohort were followed up for cancer incidence by cancer registry data. A directed acyclic graph was utilized to identify potential confounders. Multivariate Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). RESULTS: During 14-year follow-up, 1540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were detected. 8-isoprostane concentrations were positively associated with lung cancer, but not with cancer at the other sites. The HR (95% CI) for the association with lung cancer was 1.61 (1.10, 2.34) for comparison of the top with bottom tertile in total population. The association of 8-isoprostane levels with lung cancer persisted after the adjustment for smoking and other potential confounders and was multiplicative to the effect of smoking. However, 8-isoprostane levels did not improve lung cancer prediction when added to a model containing age, sex and smoking. A protective association of increasing 8-isoprostane levels was observed for prostate cancer incidence but this association was only statistically significant among current smokers. DISCUSSION: Our findings suggest that lipid peroxidation is involved in the development of lung cancer. However, high oxidative stress may be a protective factor for prostate cancer, especially among current smokers.
BACKGROUND: Urinary 8-isoprostane is an established biomarker for lipid peroxidation. However, the association between its pre-diagnostic levels and cancer incidence has rarely been evaluated. METHODS: 8793 older adults from the German ESTHER cohort were followed up for cancer incidence by cancer registry data. A directed acyclic graph was utilized to identify potential confounders. Multivariate Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). RESULTS: During 14-year follow-up, 1540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were detected. 8-isoprostane concentrations were positively associated with lung cancer, but not with cancer at the other sites. The HR (95% CI) for the association with lung cancer was 1.61 (1.10, 2.34) for comparison of the top with bottom tertile in total population. The association of 8-isoprostane levels with lung cancer persisted after the adjustment for smoking and other potential confounders and was multiplicative to the effect of smoking. However, 8-isoprostane levels did not improve lung cancer prediction when added to a model containing age, sex and smoking. A protective association of increasing 8-isoprostane levels was observed for prostate cancer incidence but this association was only statistically significant among current smokers. DISCUSSION: Our findings suggest that lipid peroxidation is involved in the development of lung cancer. However, high oxidative stress may be a protective factor for prostate cancer, especially among current smokers.
Authors: Xīn Gào; Yan Zhang; Barbara Burwinkel; Yang Xuan; Bernd Holleczek; Hermann Brenner; Ben Schöttker Journal: Clin Epigenetics Date: 2019-01-24 Impact factor: 6.551
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