Body fatness at adolescence, adult attained height and the development of tumours among persons with Lynch syndrome

World Cancer Research Fund

Plain language abstract

Background
Persons with Lynch Syndrome (LS) have an inherited mutation in certain genes, which results in a substantial increased lifetime risk of cancer. They are mainly at risk of cancer of the large bowel or of the uterus, but also of a range of other cancers, such as cancer of the ovaries, stomach, small bowel, pancreas, urinary tract, brain and possibly breast. Many of these types of cancer have convincingly been associated with greater body fatness and probably/convincingly with height in the general population. The influence of these factors on cancer risk may already start during childhood and adolescence. Linear growth and accumulation of both lean and fat tissue during that critical period, represented by height and body mass index (BMI) at age 18-20 years, has never been investigated in relation to overall cancer risk among persons with LS.
Aims and Objectives
We propose to study BMI at age 18-20 years and height in relation to risk of overall, large bowel and uterus cancer among persons with LS. In addition, we will evaluate these relationships within specific subgroups, such as in men and women separately.

How It Will Be Done
This proposed project will be carried out in an international collaboration. We will include persons with inherited mutations from at least two populations: the Geolynch cohort study and the Colon Cancer Family Registry (Colon CFR).  The Geolynch study was established in 2006 in the Netherlands and includes 486 persons with LS. Questionnaires were used to obtain information on lifestyle and health factors, such as weight at 18 years and height, smoking, medication use and physical activity. Information on the occurrence of cancer is gathered via pathology reports and medical records at the participating hospitals. The Colon CFR started in 1997 in six centres in North America and Australasia. The study includes large bowel cancer cases from population cancer registries or attendees of a family cancer clinic and their relatives. In total, 1675 persons with LS with information on weight and height were identified. Self-reported weight at 18-20 years and height were collected using personal interviews, telephone interviews or mailed questionnaires. Reported cancer diagnoses are confirmed using pathology reports, medical records, cancer registry reports and/or death certificates. Currently, 177 cancer cases are identified in Geolynch and 1117 cases in the Colon CFR. If possible, the collaboration between these two studies will be enlarged with other international LS populations. The effect of BMI at age 18-20 years and height on the occurrence of overall, large bowel and uterus cancer will be analysed with statistical methods. To investigate specific subgroups, these analyses will also be done separately for men, women, the type of gene that is mutated, and the place of recruitment.
Potential Impact
The proposed study will give us the unique opportunity to investigate the role of body fatness at adolescence and height on the occurrence of cancer among persons with LS in a large international study. The results will not only give new insights into the development of cancer, but may also provide practical tools for lifestyle advice to specific subgroups of persons with an inherited high risk of cancer.