It is estimated that approximately a third of colorectal cancer (CRC) cases are attributed to adult obesity, a modifiable risk factor, yet the obesity rates in the US stand at 38% and expected to reach 50% by 2030. While adult weight gain (20-35lbs) has been associated with increased risk of CRC, the results are inconsistent in women. Weight gain is correlated with blood glucose which is a component of the metabolic syndrome (MetS). Short term (period close to diagnosis) or long term trajectories of weight gain and blood glucose and the cumulative exposure of overweight/obesity in relation to CRC have not been assessed and is the focus of this project. Understanding the trajectories of weight gain and blood glucose in the period preceding diagnosis may improve early screening for those at highest risk and ultimately improve CRC survival. Also, assessing weight trajectories in the life course, from birth to adulthood, helps to identify time periods when weight gain is most closely associated with CRC, allowing us to target prevention services to high risk groups at important times in their lifespan. Short term trajectories of weight and blood glucose/hemoglobin A1c (HbA1c) will be assessed in a case control study design using clinical data from Regenstrief Institute, which is one of the oldest and most comprehensive data repositories in the country. In the database, 3,553 persons (men and women) diagnosed with CRC were identified, and matched on age, gender and zip code to 3,553 controls who were randomly selected from a pool of 329,551 eligible persons that have never been diagnosed with cancer. The database consists of repeat measures of weight (mean=9.5) and blood glucose (mean=11.3) in the 10 years preceding diagnosis and will be used to compare the trajectories of weight and blood glucose/HbA1c in cases and controls and estimate the odds of CRC from the trajectories, the focus of aims 1 and 2. We will also explore gender differences in the relationships between trajectories of weight and blood glucose/HbA1c and CRC risk, as well as determine if MetS in the ten years preceding diagnosis is associated with increased risk of CRC. Long term weight trajectories and their association with CRC risk will be assessed using the Nurses? Health Study II, a prospective cohort of 116,430 nurses aged 25-42 years at enrollment in 1989, the focus of aim 3. Weight at birth, early life body adiposity in age 5, 10 and 20, and biennial weight from 1989 have been reported in the NHS II study. Although parity (number of live births) reduces risk of CRC, it is associated with post-partum weight retention beyond normal weight gained with age, therefore in an exploratory aim we seek to determine if parity modifies the relationships of weight trajectories and CRC risk.
In aim 4, we will calculate cumulative years of exposure to overweight (OwY) and obesity (ObY) and estimate their association with CRC risk. Unlike previous measures, OwY and ObY, which is conceptually similar to ?pack years in smoking research?, accounts for the duration and degree/intensity of overweight and obesity. The notion of weight and blood glucose trajectories and cumulative exposure to overweight/obesity is novel and important to understand further the obesity-CRC link.
Weight gain in adulthood is an established risk factor for colorectal cancer (CRC), the third most common and the third leading cause of death in men and women, however the fluctuation patterns of weight and blood glucose in adulthood and their relation to CRC remain unknown. Understanding the trajectories of weight and blood glucose/HbA1c in the period preceding diagnosis when the cancer is developing (10-15 years) may improve early screening for CRC and ultimately CRC survival. Also, understanding life course trajectories of weight from birth to adulthood allows us to identify when weight gain and cumulative overweight/obesity are associated with CRC, so that in the future, prevention services may target the high risk groups at specific periods in the life course in an effort to reduce the impact of overweight/obesity on CRC.
