(View plain language abstract)
Increased body mass index (BMI) is an established risk factor for several cancers. There is convincing evidence for positive associations between BMI and cancers of the oesophagus (adenocarcinoma), pancreas, colon, rectum, breast (postmenopausal), endometrium, liver, kidney and probable evidence for gallbladder, ovary, and prostate. However, data is currently limited for many cancers.
Recently, a population-based cohort study of UK adults reported associations between BMI and 17 cancers, suggesting wider-ranging associations. These observations are important and need replication in other populations.
Furthermore, there is a crucial need for better characterisation of existing obesity-cancer links to determine dose-response relationships and effect modification by important individual factors across a wide range of cancers.
Another important issue is whether or not BMI alone can fully capture the complex biology underlying associations between adiposity and cancer, or whether individuals with similar BMI have distinct cancer risk depending on body fat distribution. Waist circumference (WC) is used as an indicator of central adiposity and has been suggested to be a superior cancer risk predictor.
Finally, few studies have investigated the association between overweight/obesity and cancer from a life course perspective, in part due to a lack of data on repeated weight measurements over a long duration of follow-up and sufficiently large cohort sizes.
Hypothesis and objectives
The main objective is to investigate the relationships between adiposity and 22 site-specific cancers using measured BMI and outcome data from prospectively collected primary care records in 6 million individuals from a Mediterranean population.
Specific objectives are to investigate:
- Non-linear dose-response associations and effect modification by individual factors (eg hormone use)
- Relations of duration of overweight/obesity to site-specific cancer using repeated measures of BMI
- To derive standardized risk estimates for general (BMI) and central adiposity (WC) in relation to site-specific cancers
Settings and methods
We will use information from a prospective population-based database from the Information System for the Development of Research in Primary Care (SIDIAP). SIDIAP includes anonymized patient records data for nearly six million people throughout Catalonia since 2005. SIDIAP includes all data collected by health professionals during routine visits, including anthropometric measurements, clinical diagnoses, demographic and lifestyle information. The high quality of these data has been documented. Subjects aged >=15 years with BMI data and subsequent follow-up will be included. Baseline BMI will be assigned as the earliest BMI recorded. Repeated weight measurements will be used to predict individual BMI trajectories. Approximately 429,614 first primary cancers have been recorded from 2005-2015. Hazard ratios will be calculated using Cox models, and spline models will be fitted to investigate the dose-response nature of the associations. Overweight/obesity duration will be estimated using quadratic growth models.
This project will represent one of the largest studies in this area of research to date and will substantially advance our understanding of the impact of obesity on cancer risk. It will strengthen the rationale to implement obesity prevention strategies, thereby mitigating the adverse clinical and public health effects of obesity on cancer development.