Abstract
BACKGROUND: Cumulative stress exposure is extensively involved in carcinogenesis. However, cancer risk associated with allostatic load (AL), a valid measure of chronic stress, has not been comprehensively evaluated in large cohorts, and the combined effect of AL and personality trait on cancer risk remains unknown.
METHODS: This prospective cohort study was conducted based on 245,683 participants from the UK Biobank, with a median follow-up of 13.5 years. The AL score was calculated based on 11 biomarkers. Personality traits were constructed and categorized into two clusters. Multivariable Cox regression model was used to assess the risk of incident cancer according to AL and personality clusters, and multiplicative and additive interactions were evaluated.
RESULTS: High AL was associated with an increased cancer risk compared to low AL (hazard ratio [HR] = 1.06, 95% confidence interval [CI]: 1.04-1.09), particularly for cancers of stomach, liver, kidney, esophageal, lung, colorectal, breast, and leukemia (HR ranged from 1.08 to 1.43). Personality clusters was associated with risk of lung cancer (HR = 1.14, 95% CI: 1.05-1.23), but not overall cancer. Significant synergistic interaction was observed between high AL and ‘nervous-dominant’ personality for overall cancer risk, with the strongest association observed for liver cancer (HR = 1.58, 95% CI: 1.24-2.02).
CONCLUSIONS: High AL was related to higher risks of overall cancer and site-specific cancers, particularly when combined with nervous-dominant personality, highlighting the interplay between chronic physiological stress and psychological factors in cancer development.