Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg)1,2,3
1 From the Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany (KN, SR, RK, and JL); the Department of Nutrition, Harvard School of Public Health, Boston, MA (KN); and the Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany (JL).
2 Supported by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5:"Food Quality and Safety" (contract no 513943).
3 Address correspondence to J Linseisen, Institute of Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Ingolstädter Landstr. 1, D-85746 Neuherberg, Germany. E-mail: j.linseisen@helmholtz-muenchen.de.
Background: Anticarcinogenic activities of vitamin K have been observed in animal and cell studies.
Objective: On the basis of the growth inhibitory effects of vitamin K as observed in a variety of cancer cell lines, we hypothesized that dietary intake of phylloquinone (vitamin K1) and menaquinones (vitamin K2) may be associated with overall cancer incidence and mortality.
Design: In the prospective EPIC-Heidelberg (European Prospective Investigation into Cancer and Nutrition–Heidelberg) cohort study, 24,340 participants aged 35–64 y and free of cancer at enrollment (1994–1998) were actively followed up for cancer incidence and mortality through 2008. Dietary vitamin K intake was estimated from food-frequency questionnaires completed at baseline by using HPLC-based food-composition data. Multivariate-adjusted hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards models.
Results: During a median follow-up time of >10 y, 1755 incident cancer cases occurred, of which 458 were fatal. Dietary intake of menaquinones was nonsignificantly inversely associated with overall cancer incidence (HR for the highest compared with the lowest quartile: 0.86; 95% CI: 0.73, 1.01; P for trend = 0.08), and the association was stronger for cancer mortality (HR: 0.72; 95% CI: 0.53, 0.98; P for trend = 0.03). Cancer risk reduction with increasing intake of menaquinones was more pronounced in men than in women, mainly driven by significant inverse associations with prostate (P for trend = 0.03) and lung (P for trend = 0.002) cancer. We found no association with phylloquinone intake.
Conclusion: These findings suggest that dietary intake of menaquinones, which is highly determined by the consumption of cheese, is associated with a reduced risk of incident and fatal cancer.
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