Abstract
Maintaining a healthy body weight, eating well and being physically active lowers cancer risk by 30%. However, the biology underlying these relationships is not well understood. We examined cross-sectional associations between metabolites and cancer preventive behaviors as well as the relevance to cancer-related pathways among 120 participants (50% men, mean BMI 26.6 kg/m2, mean age 54 years) with no history of smoking or cancer. Participants completed questionnaires, physical measurements and provided blood samples. Non-targeted nuclear magnetic resonance captured 223 metabolite measures. Factor analysis was performed separately for amino acid, fatty acid and lipoprotein groups. Multivariable-adjusted linear regression was used to evaluate associations between cancer preventive recommendations and metabolite-containing factors (p-value < 0.05, false discovery rate <0.20). An inflammation-related metabolite (glycoprotein acetylation) loaded strongly on a factor that was associated with excess adiposity (body fat ≥25% (men) or ≥30% (women) ß (SE) = 0.74 (0.18)) and not meeting physical activity recommendations (ß (SE) = 0.40 (0.20)). Insulin sensitivity-related metabolites including monounsaturated and polyunsaturated fats were lower among participants not meeting recommendations for adiposity, fruits and vegetables and physical activity while branched chain amino acids were higher. Cancer preventive behaviors were associated with complex metabolic signatures, including alterations in pathways known to be involved in cancer pathogenesis.
Highlights
Cancer is a global problem and the burden of cancer is growing
LP Factor 7 consisting of nine high density lipoproteins (HDL) metabolites, the ratio of apo B to A1, apo A1, nine low density lipoprotein (LDL) metabolites, and one very low density lipoprotein (VLDL) metabolite was uniquely associated with BMI, while LP Factor 8 (ten LDL, three VLDL and four intermediate density lipoprotein (IDL) metabolites) was uniquely associated with waist circumference
The exception was LP Factor 5 which consisted of VLDL, LDL and HDL of various sizes, HDL, triglycerides (TG) and the ratio of Apo B to A1, and amino acids (AA) Factor 3 for which not meeting recommendations for all three body weight measures was associated with increases in factor scores
Summary
Cancer is a global problem and the burden of cancer is growing. In 2008, there were 12.7 million new cancer cases, which is projected to reach 22.2 million by 20301. The goals of this study were to characterize the association between metabolites and cancer preventive lifestyle behaviors and to determine the potential relevance of metabolite associations to pathways known to play a role in cancer development within a cross-sectional sample of adults from a population-based cohort. These behaviors have been studied individually in previous work in specific populations[13,14,15,16], but to our knowledge, have not been investigated with respect to cancer prevention guidelines or in a Canadian cohort to determine whether associations are generalizable. A tertiary aim was to determine if findings in this middle-aged Canadian sample replicate prior evidence of metabolic associations with lifestyle behaviors
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