Background:
Obesity is a well-established risk factor for multiple cancers, including lung cancer. However, traditional metrics like Body Mass Index (BMI) fail to capture body fat distribution, a critical determinant of metabolic dysregulation. The Body Roundness Index (BRI), a novel anthropometric measure derived from waist circumference and height, better reflects visceral adiposity and associated health risks. Concurrently, the polygenic risk score (PRS) quantifies genetic susceptibility to cancer. This study aims to investigate the joint associations of BRI and PRS with lung cancer incidence and mortality and compare their predictive performance against BMI in a large prospective cohort.
Methods:
We utilized data from the UK Biobank to investigate the associations between the BRI and both lung cancer incidence and cancer mortality. BRI was calculated according to the following formula: BRI = 364.2 - 365.5 × √ (1 - (waist circumference / (2π)) ²/ (height / 2) ²). PRS for lung cancer were derived using genome-wide significant SNPs (p < 5×10??), weighted by effect sizes from prior GWAS. Participants were categorized into three groups based on BRI and PRS quintiles. Cox proportional hazards models were used to evaluate the relationships between BRI and these outcomes. To evaluate the predictive capabilities of BRI and BMI for cancer outcomes, receiver operating characteristic (ROC) analysis and area under the curve (AUC) metrics were employed. The DeLong test was used to statistically compare the AUCs of BRI and BMI.
Results:
This study included 442,525 participants, among whom 4,083 lung cancer cases and 2,902 lung cancer-related deaths were identified. After adjusting for age, sex, ethnicity, education level, smoking status, alcohol consumption, and family history of cancer, individuals in third quintile (Q3: 4.58 to 23.55) had a 1.16-fold (95% CI: 1.07 – 1.26) increased risk of lung cancer incidence and a 1.13-fold (95% CI: 1.03 – 1.25) higher risk of lung cancer mortality compared to those in the lowest quintile (Q1: -1.08 to 3.36). In the high-risk PRS group, individuals in the third quintile of BRI had a 1.21-fold (95% CI: 1.06–1.37) higher risk of lung cancer incidence and a 1.17-fold (95% CI: 1.01–1.36) increased risk of lung cancer mortality compared to those in the lowest BRI quintile. ROC analysis indicated that the combination of BRI and PRS (AUC incidence= 0.58, AUC mortality= 0.58) outperformed the combination of BMI and PRS (AUC incidence = 0.51, AUC mortality= 0.51) in predicting both lung cancer incidence and mortality (p < 0.05).
Conclusion:
BRI is a stronger predictor of lung cancer incidence and mortality than BMI, with enhanced discrimination when combined with PRS. These findings support integrating BRI and genetic risk for precision risk stratification, potentially guiding targeted prevention strategies.