Approved research

Obesity, body shape, nutrition, hypertension, steroid hormones and vitamin D: associations, interactions and contribution to metabolic health and the risk of cancer development and survival

Lay summary

Obesity and diabetes are well-recognized risk factors for various cancers. Some obese individuals, however, do not show diabetes-type complications, but it is unclear how this impacts cancer risk. High blood pressure is also related to some types of cancers, but its influence on others is less known. Fat accumulation around the waist is a key factor linking diet, obesity, diabetes and high blood pressure. Recently-developed body-shape indices for waist and hip measures have shown stronger associations with diabetes, heart disease and the risk of death than body-mass index or waist measures alone, but their relevance to cancer risk is unknown. Obesity, body-shape and high blood pressure are linked to steroids such as testosterone, estrogens and cortisol. Steroids play an important role in fat mass distribution. The different body shapes of men and women are partly determined by sex steroids. Further, cortisol increase leads to fat accumulation around the waist, diabetes and high blood pressure. The production of another steroid, aldosterone, is affected in obesity. When increased, aldosterone can lead to diabetes and high blood pressure. Another steroid, Vitamin D, has shown protective effect for heart disease and some cancers. We propose, for the duration of three years, to perform genetic studies to identify common genetic variants related to body-shape indices and blood levels of vitamin D and to examine overlaps with genetic variants related to body-mass index, waist and hip measures and steroids. Further, we would like to study the relationships and interactions between body-shape indices (including genetic variants); components of the diet; genetic variants of steroid-related genes; blood levels of vitamin D (including genetic variants), diabetes-like complications and high blood pressure (also considering the type of drugs used for treatment) and how these relate to the risk of developing cancer and dying from it (overall and by organ, stage, cancer characteristics and type of treatment). We would also explore how body-shape indices relate to computer measurements of fat accumulation. Clarifying the role of fat distribution in cancer and uncovering potential interactions with high blood pressure, general obesity and diabetes could be of great importance for public health, as these all are widespread with increasing age. Further, vitamin D deficiency is common. Convincing evidence for a protective effect on cancer could affect the use of vitamin-D-containing drugs. Results from the genetic studies would provide strong evidence regarding the genetic variability related to body shape and blood levels of vitamin D.