Cancer-related genes and pathways have recently been implicated in a genome-wide meta-analysis of head size. In the current study, we aimed to evaluate the association between adult head circumference and the risk of cancer. This is a cohort study using data from the Hong Kong Osteoporosis Study, where 1,301 participants aged 27-96years with head circumference measured between 2015 and 2019, and without a history of cancer, were followed up to 15 January 2024. Incident cancers were identified using electronic medical records from a territory-wide database. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression, adjusting for age, sex, height, weight, education, smoking, alcohol drinking, physical activity, and family history of cancer, as well as accounting for familial clustering. The median head circumference was 53cm (interquartile range [IQR]: 51-54) and 54cm (IQR: 53-55) for women and men, respectively. During a median follow-up of 6.9years, 66 individuals were diagnosed with cancer. In the adjusted model, a larger head circumference was associated with an increased risk of any cancer (HR per cm increase: 1.17; 95% CI 1.00-1.36). Results remained similar when adjusting for waist-to-hip ratio instead of weight or when additionally adjusting for serum calcium and phosphorus levels. When stratified by cancer sites, head circumference was most strongly associated with colorectal cancer (HR per cm increase: 1.81; 95% CI 1.14-2.90) and prostate cancer (HR per cm increase: 1.58; 95% CI 1.16-2.16). Head circumference is positively associated with the risk of cancer independently of height, weight, and other cancer risk factors.
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