Diet, lifestyle, antioxidants, and biomarkers of cancer risk - an epidemiological report from the Malmö Diet and Cancer cohort

Abstract: This thesis examines associations between a number of epidemiological or biological markers of cancer risk and oxidative stress, in order to achieve a better understanding of how diet, lifestyle, and genetic factors contribute to the occurrence of oxidative stress. Data from the Malmö Diet and Cancer (MDC) cohort was used. The MDC study is a population-based cohort study which uses a detailed modified diet history method for dietary assessment. It includes an extensive sociodemographic/lifestyle questionnaire, body composition measurement by bioimpedance, and a biological bank of separated blood components. In one sub-sample, consisting of 15,137 men and women aged 46-68 years, low fruit and vegetable consumption was significantly associated with several established risk markers of cancer, e.g. low educational level, high alcohol consumption, and smoking. Another sub-sample, consisting of 544 men and women aged 46-67 years, was used for studies on serum levels of the antioxidant nutrients ?-carotene and ?-tocopherol, and on autoantibody (aAb) titres against 5-hydroxymethyl-2’deoxyuridine (5-HMdU), an oxidized DNA base derivative. The serum nutrient levels were associated with body fat, smoking, and intake of several antioxidant nutrients. However, ?-carotene was negatively associated with total body fat, while ?-tocopherol was positively associated, particularly with centrally distributed fat. ?-carotene was moderately associated with carrot and leafy vegetable consumption in non-smokers, and with ?-carotene supplements and (more unexpectedly) with coffee in smokers. ?-tocopherol levels were associated with vitamin E supplements only. High anti-5-HMdU aAb titres were associated with high alcohol consumption, with smoking in combination with null genotype for the antioxidative enzyme glutathione S-transferase M1 (GSTM1), and, in men, with high body fat percentage. The aAb titres were not associated with consumption of fruits or vegetables. The conclusions are as follows. Fruit and vegetable consumption may confound the associations between cancer risk and other risk markers of cancer. The hypothesis of functional synergisms between antioxidants in the body and dietary antioxidants receives some support from these results. Anti-5-HMdU aAb titre may not be a pure marker of either oxidative stress or immune function, but rather of an equilibrium between disposition to produce IgM and oxidative stress. Oxidative-antioxidative status in humans is probably determined by interactions between nutritional, genetic, metabolic, behavioural, and sociodemographic factors.