Body mass index and the risk of subsequent cancers among older cancer survivors.
Authors: Bodelon Clara , Sung Hyuna , Mitchell Ellen , Deubler Emily L , Newton Christina C , Jemal Ahmedin , Teras Lauren R. , Patel Alpa 
Published: June 2024

12043 Background: Little is known about the etiology of second primary cancers among survivors of older adult-onset cancers. Descriptive studies have suggested that lifestyle factors, including body mass index (BMI), may be important. Here we investigated whether BMI is associated with the risk of a subsequent malignancy among older adult cancer survivors. Methods: This analysis was conducted among men and women enrolled in the Cancer Prevention Study II Nutrition cohort who were diagnosed with a first non-metastatic incident cancer between 1992 and 2015. Survivors were followed-up until 2017 for the diagnosis of a subsequent primary malignancy at a different organ to avoid the inclusion of recurrences, as their etiology may differ. Analyses were restricted to those who were younger than 85 years at their initial diagnosis. Subsequent malignancies were included if they were diagnosed at least 60 days after the first cancer. Outcomes of interest were second cancers and obesity-related second cancer as defined by the IARC. BMI at the time or before their first cancer was self-reported (median: 1.3 years from BMI report to diagnosis). Participants who were underweight (BMI<18.5 kg/m2) were excluded. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) to estimate the risk of second cancers associated with BMI. Models were adjusted for age, sex, race, diagnosis year, and stage of the first cancer. Results: This cohort included 26,894 participants diagnosed with a first cancer. The median age at diagnosis of the first cancer was 72.5 years (interquartile range (IQR): 67.7, 77.0). Most participants were women (59%), overweight or obese (60%) and diagnosed with localized disease (71%). During a median of follow-up of 7.5 years (IQR: 3.2, 13.1), 3,748 participants were diagnosed with a second cancer, including 1,140 obesity-related second cancers. Approximately 90% of second malignancies were diagnosed at least 1 year, and 70% at least 5 years after the first cancer. Compared with cancer survivors whose BMI was in the normal range (18.5≤BMI<25), those who were overweight or obese were at an increased risk of any second cancer (25≤BMI<30: HR=1.12, 95% CI: 1.05, 1.21; BMI≥30: HR=1.29, 95% CI: 1.18, 1.42) and BMI-related cancers (25≤BMI<30: HR=1.37, 95% CI: 1.20, 1.57; BMI≥30: HR=1.60, 95% CI: 1.36, 1.88). In particular, obesity was associated with increased risks of breast (HR=1.43, 95% CI: 1.03, 1.98) and colorectal (HR=1.91, 95% CI: 1.42, 1.56) second cancers. Conclusions: Older adult cancer survivors who were overweight or obese at the time of their first cancer diagnosis were at higher risk of developing a second cancer, especially a BMI-related cancer. These findings have important public health implications given the high prevalence of overweight and obesity in this population. Weight loss strategies should be considered and heightened awareness of second cancers among physicians of older cancer survivors.