Background/ObjectivesPhysical activity (PA) protects against a wide range of diseases. Habitual PA appears to be heritable, motivating the search for specific genetic variants that may inform efforts to promote PA and target the best type of PA for each individual.Subjects/MethodsWe used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (nmax=377,234) and two measures based on wrist-worn accelerometry data (nmax=91,084). We examined genetic correlations of PA with other traits and diseases, as well as tissue-specific gene expression patterns. With data from the Atherosclerosis Risk in Communities (ARIC; n=8,556) study, we performed a meta-analysis of our top hits for moderate-to-vigorous PA (MVPA).ResultsWe identified ten loci across all PA measures that were significant in both a basic and a fully adjusted model (p<5 × 10−9). Upon meta-analysis of the nine top hits for MVPA with results from ARIC, eight were genome-wide significant. Interestingly, among these, the rs429358 variant in the APOE gene was the most strongly associated with MVPA, whereby the allele associated with higher Alzheimer’s risk was associated with greater MVPA. However, we were not able to rule out possible selection bias underlying this result. Variants in CADM2, a gene previously implicated in obesity, risk-taking behavior and other traits, were found to be associated with habitual PA. We also identified three loci consistently associated (p<5 × 10−5) with PA across both self-report and accelerometry, including CADM2. We find genetic correlations of PA with educational attainment, chronotype, psychiatric traits, and obesity-related traits. Tissue enrichment analyses implicate the brain and pituitary gland as locations where PA-associated loci may exert their actions.ConclusionsThese results provide new insight into the genetic basis of habitual PA, and the genetic links connecting PA with other traits and diseases.

Overweight status is common among women breast cancer survivors and places them at greater risk for metabolic disorders, cardiovascular morbidity, and breast cancer recurrence than nonoverweight survivors. Efforts to promote weight control in this population are needed. The objective of this research was to evaluate the effect of low-fat or low-carbohydrate diet counseling on weight loss, body composition, and changes in metabolic indexes in overweight postmenopausal breast cancer survivors. Survivors (n = 40) were randomized to receive dietitian counseling for a low-fat or a reduced carbohydrate diet for 6 mo. Weight and metabolic measures, including glucose, insulin, HbA1c, HOMA, lipids, hsCRP, as well as blood pressure were measured at baseline, 6, 12 and 24 wk. Dietary intake of fat and carbohydrate was reduced by 24 and 76 g/day, respectively. Weight loss averaged 6.1 (± 4.8 kg) at 24 wk and was not significantly different by diet group; loss of lean mass was also demonstrated. All subjects demonstrated improvements in total/HDL cholesterol ratio, and significant reductions in HbA1c, insulin, and HOMA. Triglycerides levels were significantly reduced only in the low-carbohydrate diet group (-31.1 ± 36.6; P = 0.01). Significant improvements in weight and metabolic indexes can be demonstrated among overweight breast cancer survivors adherent to either a carbohydrate- or fat-restricted diet.

Background Incidence rates of non-Hodgkin’s lymphoma (NHL) increased substantially in the United States and worldwide during the latter part of the 20th century, but little is known about its etiology. Obesity is associated with impaired immune function through which it may influence the risk of NHL; other factors reflecting energy homeostasis (height, abdominal adiposity, and physical activity) may also be involved. Methods We examined the association of anthropometric factors and physical activity with risk of NHL and its major subtypes in a large cohort of women aged 50–79 years old who were enrolled at 40 clinical centers in the United States between 1993 and 1998. Over a mean follow-up period of 11 years, 1123 cases of NHL were identified among 158,975 women. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results Height at baseline was positively associated with risk of all NHL and with that of diffuse large B-cell lymphoma (HRsq4vs.q1 1.19, 95% CI 1.00–1.43 and 1.43, 95% CI 1.01–2.03, respectively). Measures of obesity and abdominal adiposity at baseline were not associated with risk. Hazard ratios for NHL were increased for women in the highest quartile of weight and body mass index at age 18 (HRsq4vs.q1 1.29, 95% CI 1.01–1.65 and 1.27, 95% CI 1.01–1.59, respectively). Some measures of recreational physical activity were modestly associated with increased risk of NHL overall, but there were no clear associations with specific subtypes. Conclusion Our findings regarding anthropometric measures are consistent with those of several previous reports, suggesting that early life influences on growth and immune function may influence the risk of NHL later in life.

Background-Overweight status after breast cancer treatment may increase a woman's risk for recurrent disease and/or early onset cardiovascular disease. Green tea has been proposed to promote weight loss and favourably modify glucose, insulin and blood lipids. This pilot study tested the effect of daily decaffeinated green tea consumption for 6 months on weight and body composition, select metabolic parameters, and lipid profiles in overweight breast cancer survivors.

In our sample, overweight breast cancer survivors commonly have MetS and elevated CRP that place them at increased risk for cardiovascular and other metabolic diseases. If replicated in a larger sample, this warrants close medical monitoring to prevent and reduce morbidity and mortality unrelated to breast cancer.

Background: Prospective studies in Western and Asian populations suggest that height is a risk factor for various cancers. However, few studies have explored potential confounding or effect modification of the association by other factors.Methods: We examined the association between height measured at enrollment in 144,701 women participating in the Women's Health Initiative and risk of all cancers combined and cancer at 19 specific sites. Over a median follow-up of 12.0 years, 20,928 incident cancers were identified. We used Cox proportional hazards models to estimate HR and 95% confidence intervals (CI) per 10 cm increase in height, with adjustment for established risk factors. We also examined potential effect modification of the association with all cancer and specific cancers.Results: Height was significantly positively associated with risk of all cancers (HR ¼ 1.13; 95% CI, 1.11-1.16), as well as with cancers of the thyroid, rectum, kidney, endometrium, colorectum, colon, ovary, and breast, and with multiple myeloma and melanoma (range of HRs: 1.13 for breast cancer to 1.29 for multiple myeloma and thyroid cancer). These associations were generally insensitive to adjustment for confounders, and there was little evidence of effect modification.Conclusions: This study confirms the positive association of height with risk of all cancers and a substantial number of cancer sites.Impact: Identification of single-nucleotide polymorphisms associated both with height and with increased cancer risk may help elucidate the association. Cancer Epidemiol Biomarkers Prev; 22(8); 1353-63. Ó2013 AACR.

Genetic variations in the adrenergic receptor (ADR) have been associated with body composition in cross-sectional studies. Recent findings suggest that ADR variants may also modify body composition response to lifestyle. We assessed the role of ADR variants in body composition response to 12 months of resistance training versus control in previously sedentary postmenopausal women. Randomized trial completers were genotyped for A2BGlu9/12 by fragment length analysis, and B2Gln27Glu and B3Trp64Arg by TaqMan (n=148, 54% hormone therapy users). Associations between genotypes and body composition, by dual energy X-ray absorptiometry, were analyzed using univariate models. There was no main effect of individual genes on change in body composition, however, gene × exercise interactions were observed for A2BGlu9/12 and B2Gln27Glu on change in lean soft tissue (LST, p=0.02); exercisers on the A2BGlu9- background gained LST compared to a loss among controls over 12 months (p<0.05), with no significant intervention effect on the A2B Glu9+ background. Similarly, there was a significant LST gain with exercise on the B2Glu27+ background compared to loss among controls and no intervention effect on the B2Glu27- background. A non-significant association between total body fat (TBF) and B3Trp64Arg persisted among sedentary controls only when intervention groups were separated (%TBF gain with B3Arg 64+ carriage, p=0.03); exercisers lost TBF regardless of genotype. In summary, effect modification by lifestyle was demonstrated on ADR A2B, B2, and B3 genetic backgrounds. Individuals with certain ADR genotypes may be more vulnerable to adverse changes in body composition with sedentary behavior, thus these candidate genes warrant further study.

Aim Few epidemiological studies have investigated the association between circulating concentrations of the active vitamin D metabolite 1,25(OH)2D and metabolic syndrome. We sought to determine whether blood levels of 1,25(OH)2D are associated with metabolic syndrome and its individual components, including waist circumference, triglycerides, blood pressure, and glucose, and high-density lipoprotein. We also investigated these associations for the more abundant precursor vitamin D metabolite, 25(OH)D. Methods Participants from two completed clinical trials of colorectal neoplasia with available metabolic syndrome data and blood samples for measurement of 1,25(OH)2D (n=1048) and 25(OH)D (n=2096) were included. Cross-sectional analyses of the association between concentrations of 1,25(OH)2D, 25(OH)D, metabolic syndrome, and its components were conducted. Results A statistically significant inverse association was observed for circulating concentrations of 1,25(OH)2D and metabolic syndrome, with adjusted ORs (95% CIs) of 0.73 (0.52–1.04) and 0.52 (0.36–0.75) for the second and third tertiles of 1,25(OH)2D, respectively (p-trend <0.001). Significant inverse relationships were also observed between 1,25(OH)2D and high triglycerides (p-trend <0.001), and low high-density lipoprotein (p-trend <0.001). For 25(OH)D concentrations, significant inverse associations were found for metabolic syndrome (p-trend <0.01), high waist circumference (p-trend<0.04) and triglyceride levels (p-trend <0.01). Participants with 25(OH)D ≥ 30 ng/ml and in the highest tertile of 1,25(OH)2D demonstrated significantly lower odds of metabolic syndrome, with an OR (95% CI) of 0.38 (0.19–0.75) compared to those in the lowest category for both metabolites. Conclusion These results provide new evidence that the relatively rarely-studied active hormonal form of vitamin D, 1,25(OH)2D, is associated with metabolic syndrome and its components, and confirm prior findings for 25(OH)D. The finding that 1,25(OH)2D is related to high-density lipoprotein, while 25(OH)D is not, suggests that there may be an independent mechanism of action for 1,25(OH)2D in relation to metabolic dysregulation.