Associations between adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and biomarkers of inflammation, hormonal, and insulin response

Abstract

Adherence to the 2007 WCRF/AICR cancer prevention recommendations has been associated with lower cancer risk but the underlying biological mechanisms have not been elucidated. We utilized dietary and lifestyle data from 11,342 women in the Nurses' Health Study and 8,136 men in the Health Professionals Follow-up Study, to investigate associations between adherence scores and markers of inflammation, hormonal and insulin response. Two scores ranging from 0 to 3 were constructed to assess adherence to the energy balance-related recommendations (weight management, physical activity, energy density); and the plant, animal foods and alcohol intake recommendations; with higher scores indicating greater adherence. The following biomarkers were assessed in plasma samples donated by chronic disease-free women (1990) and men (1994): C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α receptor 2 (TNFαR2) and adiponectin for inflammation; estrone and estradiol for hormonal response in women, C-peptide for hyperinsulinemia; and triglycerides/high density lipoprotein-cholesterol (TG/HDL) ratio for insulin resistance. In multivariable-adjusted linear regression analyses, we estimated relative concentrations of biomarkers across adherence categories. There was a significant trend of lower (higher for adiponectin) biomarker concentrations with higher adherence to the energy balance recommendations (all p trend <0.0001). Comparing the highest (3) to the lowest recommendation category (0-1), the percent difference in relative concentrations of biomarkers was CRP, -69%; IL6, -41%; TNFαR2, -13%; adiponectin, +36%; C-peptide, -43%; TG/HDL, -43%; estrone, -31%; and estradiol, -43%; in women; and CRP, -59%; IL6, -42%; TNFαR2, -10%; adiponectin, +22%; C-peptide, -44%; and TG/HDL, -40%; in men. In contrast, associations between adherence to the plant, animal foods and alcohol intake recommendations and biomarker concentrations were weaker, and mostly nonsignificant. The healthier biomarker profile associated with greater adherence to the WCRF/AICR cancer prevention recommendations is driven mainly by adherence to the energy balance-related recommendations.

Keywords: WCRF/AICR recommendations; cancer prevention; chronic inflammation; diet; hormones; hyperinsulinemia; insulin resistance; lifestyle.

Figure 1

Multivariable-adjusted percent changes in the relative concentrations of plasma inflammation markers (95% confidence intervals) across adherence categories of (A) the energy balance-related recommendations (BMI, physical activity and energy density), and (B) the combined plant/animal food/alcohol intake recommendations in the Nurses’ Health Study (women), 1990; and Health Professional Follow-up Study (men), 1994. 0–1 was the lowest or least adherent category (reference) while 3 was the highest or most adherent category. CRP=C-reactive protein, IL6=interleukin-6, TNFαR2=tumor necrosis factor alpha receptor 2. Biomarker concentrations were adjusted for regular aspirin/NSAID use, age at blood draw, smoking status, physical activity, case-control status, postmenopausal status, postmenopausal hormone use, and chronic diseases/conditions. The following chronic diseases/conditions (yes=1/no=0) were included in the score: hypercholesterolemia, cancer, diabetes, high blood pressure, heart disease, and rheumatoid/other arthritis). The P-value for trend was the P-value of the combined recommendation score as a continuous variable adjusted for all covariates previously listed. Biomarker sample sizes were different: in women, n=3,550 for all four inflammatory markers. In men; CRP, n=5,157; IL6, n=3,044; TNFαR2, n=4,072; and adiponectin, n=4,348.

Figure 2

Multivariable-adjusted percent changes in the relative concentrations of plasma markers of insulin response and hormonal response (95% confidence intervals) across adherence categories of (A) the energy balance-related recommendations (BMI, physical activity and energy density), and (B) the combined plant/animal food/alcohol intake recommendations in the Nurses’ Health Study (women), 1990; and Health Professional Follow-up Study (men), 1994. 0–1 was the lowest or least adherent category (reference) while 3 was the highest or most adherent category. CPEP=C-peptide, TG/HDL=triglyceride/high density lipoprotein ratio. Estrone and estradiol were examined only among postmenopausal women not using exogenous hormones. Biomarker concentrations were adjusted for regular aspirin/NSAID use, age at blood draw, smoking status, physical activity, case-control status, postmenopausal status, postmenopausal hormone use, and chronic diseases/conditions. The following chronic diseases/conditions (yes=1/no=0) were included in the score: hypercholesterolemia, cancer, diabetes, high blood pressure, heart disease, and rheumatoid/other arthritis). The P-value for trend was the P-value of the combined recommendation score as a continuous variable adjusted for all covariates previously listed. Biomarker sample sizes were different: in women; CPEP, n=5,834; TG/HDL, n=3,826; estrone, n=1,217; and estradiol, n=1,254. In men; CPEP, n=3,955; and TG/HDL, n=3,575.