Obesity Clinical Trial
Official title:
Diet, Adiposity, and Metabolic Alterations: a Prospective Observational Study of Three US Cohorts
Obesity is associated with increased risk of several cancers. Suggested mechanisms mediating the obesity-cancer associations include hyperinsulinemia and altered IGF signaling, changes in sex hormone levels as well as altered secretion of adipokines and inflammatory proteins. However, little is known about the influence of lifetime adiposity on the relevant biomarkers. Moreover, although diet has been suggested to ameliorate the adverse metabolic effects of obesity, convincing evidence regarding how dietary factors may influence obesity-related carcinogenic pathways remains lacking. Thus, in the current project, the investigators aim to 1) examine the associations between trajectories of body fatness and plasma biomarker levels of the insulin/IGF system, sex hormones and biomarkers of inflammatory response including adipokines; 2) investigate how nutritional factors may modulate these obesity-related biomarkers. The investigators propose to utilize two large ongoing cohorts of US men and women, the Nurses' Health Study and Health Professionals Follow-up Study.
According to the International Agency for Research on Cancer (IARC), there is sufficient
evidence that avoidance of weight gain reduces the risk of several cancers, including
colorectal, breast (postmenopause), pancreatic, endometrial, kidney (renal-cell), liver,
gallbladder, oesophageal (adenocarcinoma), multiple myeloma, meningioma, ovarian, thyroid and
stomach (cardia) cancer. Several mechanisms have been suggested to mediate the obesity-cancer
association, including increased insulin levels and bioavailability of insulin-like growth
factor (IGF)-1, low-grade chronic inflammation, and changes in sex hormone levels.
In previous studies, the investigators have identified five heterogeneous trajectory groups
of body fatness from age five and up to 60 years (lean-stable, lean-moderate increase,
lean-marked increase, medium-stable, and heavy-stable/increase). These trajectories have been
associated with distinct patterns of cancer incidence and mortality. Having excess body
weight at any life period have been associated with increased risk of total and obesity
related cancers. How the various trajectories of body shape relate to cancer relevant risk
biomarkers is however yet to be determined.
To gain a better understanding of the complex interplay between obesity, obesity-related risk
biomarkers and cancer development, the investigators aim to examine the associations between
trajectories of body fatness and cancer relevant risk biomarkers in the Nurses' Health Study
and Health Professionals Follow-up Study. Moreover, the investigators will examine how
nutritional factors, such coffee intake, may modulate the levels of these biomarkers.
The investigators hypothesize that in general individuals who have excess body weight at any
life period will have a more unfavorable biomarker profile than those who are lean across the
lifespan, although a different pattern may be expected for some markers. Also, the
investigators hypothesize that some nutritional factors, such high intake of coffee, may
ameliorate the adverse metabolic effects of obesity by modulating the levels of these
biomarkers.
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