Depressive symptoms, depressive symptom trajectories, and the risk of cancer in middle-aged and older people: evidence from the China Health and Retirement Longitudinal Study (CHARLS) (2011–2020)

Background: Depression or depressive symptoms have been hypothesized as a risk factor for cancer incidence, and a load of studies have investigated the link between depression or depressive symptoms, depressive symptom history, and cancer incidence. However, whether depressive symptoms or depressive symptom history are associated with cancer incidence has not reached a consistent conclusion, and there is a lack of studies on the relationship between depressive symptom trajectories and new cancers. To address the research gaps, we aimed to investigate the association of depressive symptoms, depressive symptom trajectories, and the risk of cancer in middle-aged and older people in China. Methods: We analyzed the survey data on depressive symptoms and cancers collected from 2011 to 2020 in the China Health And Retirement Longitudinal Study (CHARLS), where depressive symptoms were measured by the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Cox proportional hazards models were constructed to estimate relative hazards for new cancers (2013-2020) among participants with depressive symptoms in 2011, with results being adjusted for age, gender, education level, area of residence, marital status, household income, smoking status, drinking status, body mass index (BMI), diabetes, and cardiovascular disease (CVD). Meanwhile, the group-based trajectory modeling approach was used to capture the depressive symptom trajectories among participants without cancers from 2011 to 2018, and logistic regression models were applied to explore the association between trajectories and cancer incidence. New cancers in 2020 were considered positive outcomes in this regression model, and the adjusted variables were the same as those in the Cox models. Findings: There were 9557 participants without cancer in 2011, where 3500 had depressive symptoms and 6057 without depressive symptoms. For all participants included in the Cox regression analysis, there were 269 new cancers from 2013 to 2020. Cox regression analysis showed there was no association between depressive symptoms and cancer incidence. Additionally, 6749 participants without cancers from 2011 to 2018 were included for depressive symptom trajectory analysis, and four trajectories with distinct characteristics were identified. We named the four trajectories ‘continuous mild,’ ‘continuous moderate,’ ‘gradually increasing,’ and ‘continuous severe.’ Among them, the ‘continuous severe’ trajectory was associated with an increased risk of cancer incidence (p=0.011). Interpretation: This is the first study in China exploring the link between cross-sectional depressive symptoms, depressive symptom trajectories over time, and new cancers. Consistent with most existing studies, we found that cross-sectional depression symptoms had no associations with new cancers. Significantly, we discovered that the trajectory of continuous severe depressive symptoms was associated with cancer incidence. This study's findings indicate that specific interventions should be taken for middle-aged and older people with continuous severe depressive symptoms in China to reduce the risk of cancer incidence. Future studies need to focus on specific cancer types. Funding: Humanities and Social Science Project of the Ministry of Education of China [22YJA630036].