title: Plasma 7beta-hydroxycholesterol as a possible predictor of lung cancer risk.
abstract: 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 7beta-hydroxycholesterol was associated with lung cancer risk. The high crude risk estimate (OR approximately equals 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 7beta-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 7beta-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 7beta-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.
authors.affiliation: German Cancer Research Centre, Division of Clinical Epidemiology, Heidelberg, Germany. j.linseisen@wzw.tum.de
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Günther
authors.initials: G
authors.lastname: Wolfram
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Miller
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000453:epidemiology / Q000473:pathology; D000328:Adult; D017677:Age Distribution; D014408:Biomarkers, Tumor / Q000097:blood; D018288:Carcinoma, Small Cell / Q000097:blood / Q000453:epidemiology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000453:epidemiology / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D015994:Incidence; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012016:Reference Values; D018570:Risk Assessment; D012307:Risk Factors; D012494:Sampling Studies; D017678:Sex Distribution; D012907:Smoking / Q000009:adverse effects*
chemical_list: D014408:Biomarkers, Tumor; D006888:Hydroxycholesterols