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Plasma 7ß-Hydroxycholesterol as a Possible Predictor of Lung Cancer Risk¹

German Cancer Research Centre, Division of Clinical Epidemiology, Heidelberg, Germany [J. L., A. B. M.]; Unit of Human Nutrition and Cancer Prevention, Technical University of Munich, 85350 Freising, Germany [J. L.]; and Chair of Human Nutrition, Life Science Center Weihenstephan, Technical University of Munich, 85350 Freising, Germany [G. W.]

Epidemiological data suggests a role of dietary cholesterol in the etiology of lung cancer without having a clear biological hypothesis. Although smoking as the outstanding risk factor for lung cancer may enhance lipid peroxidation reactions, this study was planned to assess smoking-independent associations between the extent of cholesterol oxidation and the risk for lung cancer. In the frame of a nested case-control study in European Prospective Investigation on Cancer-Heidelberg, six cholesterol oxidation products (COPs) were determined in plasma samples of 20 incident lung cancer patients obtained 1.9 ± 0.6 years before diagnosis and in 40 matched (including smoking habits) controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression. Among all COP compounds tested, plasma 7ß-hydroxycholesterol was associated with lung cancer risk. The high crude risk estimate (OR 5) became significant after adjustment for sports activity (OR = 6.83, CI = 1.08–43.01, 3rd versus 1st tertile). For the independent effect of 7ß-hydroxycholesterol, i.e., adjusted for other COP compounds, an OR of 8.08 (CI = 1.12–58.54, 3rd versus 1st tertile) was calculated (P = 0.04 for trend). Lung cancer risk adjusted for sports activity significantly increased by 26% (CI = 1.050–1.506, P = 0.01) per unit (1 nmol/mmol plasma cholesterol) of 7ß-hydroxycholesterol. No dietary factor had a significant effect in the regression model, but the dietary intake of meat, eggs, animal fat, cholesterol, and fruits (inversely) correlated with plasma COP concentrations. In this small study, plasma 7ß-hydroxycholesterol appeared to be a smoking-independent predictor of lung cancer risk and might therefore be used as a biomarker. Because of the rather high-risk estimate, research on possible intrinsic biological effects of this compound should be encouraged.