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Body and adipose tissue composition and risk of obesity-related cancers

Body and adipose tissue composition and risk of obesity-related cancers

Principal Investigator: Dr Thomas Rohan
Approved Research ID: 70902
Approval date: March 31st 2021

Lay summary

The aim of the study is to examine the association between adipose tissue composition and the risk of obesity-related cancers. Obesity has been related to risk of several types of cancer. Body mass index (BMI) has been used as surrogate measurement of body fat to estimate obesity-related risk of several types of cancer such as those of the colorectum, liver, pancreas, ovary, endometrium and postmenopausal breast.

However, although BMI correlates with adipose tissue mass, it cannot distinguish between lean muscle and fat volume. A growing body of evidence has indicated that adipose tissue, and in particular excessive abdominal fat, affects several metabolic mechanisms and promotes tumorigenesis in the overweight and obese. Visceral fat is more strongly correlated with metabolic changes that are associated with an increased risk of some obesity-related types of cancer. It is unclear, however, whether adipose tissue composition contributes to obesity-related cancer risk. New methodologies, such as magnetic resonance imaging (MRI), provide measures of different types of adipose tissue depots in the body. MRI is costly and not easily available in the clinical setting.

This highlights the importance of ongoing UK Biobank multi-modal imaging study, which is the world's largest study of this kind, designed with the purpose of collecting MRI data from 100,000 individuals already enrolled in the UK Biobank. We propose to use all MRI data on adipose tissue, with a focus on the variables representing fat composition in the abdominal region, already available or that will be collected by the study, and to relate these measures to risk of obesity-related cancer occurrence. We will also take into account other relevant factors, using the extensive information on demographic, medical and lifestyle risk factors available in the UK Biobank study.

The results will provide a unique contribution to the knowledge on the obesity-cancer risk relationship and may help to improve strategies to reduce the risk of certain types of cancer.

Current scope

1) We will examine the associations between MRI-derived estimates of adipose tissue with emphasis on the proportion of visceral and subcutaneous fat and risk of developing obesity-related cancers overall and according to histological subtypes of specific cancers among participants in the UK Biobank imaging study.

2) We will examine the association of ratio of the two components of abdominal adipose tissue (visceral and subcutaneous) and several obese-related cancers.

3) We will examine the aforementioned associations by body mass index predefined categories (normal, overweight and obese).

Scope Extention

4) We will evaluate the association between the levels of multiple metabolites with visceral and subcutaneous abdominal fat, their ratio, intra-hepatic fat, and peripheral muscle fat infiltration quantified by MRI. We plan to examine the association between serum concentrations of several biomarkers including lipoproteins, fatty acids, liver enzymes, amino acids, glycolysis metabolites, and sex hormones obtained at enrollment in UK Biobank study participants, and from a repeat assessment in 2012-2013 in a sample of 20,000 participants who were invited for a follow-up exam in those subjects with available MRI measures. Correlation analysis will be adjusted for demographic and lifestyle risk factors. Additional analytical approaches would be utilized to identify biomarker indicators of adipose tissue distribution.

5) We will test the aforementioned associations by body mass index predefined categories (normal, overweight and obese) and diabetes status.

New scope of the study

A healthy lifestyle index, calculated by combining scores for several modifiable factors such as quality of diet, level of physical activity, cigarette smoking, alcohol intake, body mass index, and waist circumference, has been associated with the risk of several chronic disease.

We would to investigate 1) the relationship between a healthy lifestyle index and several indicators of adipose tissue distribution, and in particular, abdominal visceral and subcutaneous fat, intra-hepatic fat, and peripheral muscle fat infiltration, as quantified by MRI; we propose to conduct these analyses in the whole MRI cohort, and separately in men and women (the latter group, overall and by menopausal status); and 2) whether such relationships differ by levels of  body mass index.