Genetic Risk, Health-Associated Lifestyle, and Risk of Early-onset Total Cancer and Breast Cancer

Area of Science:

• Oncology
• Genetics
• Preventive Medicine

Background:

• Early-onset cancer, diagnosed before age 50, presents aggressive characteristics and rising incidence globally.
• The interplay between genetic predisposition, lifestyle factors, and early-onset cancer risk remains largely unexplored.

Approach:

• A prospective cohort study analyzed 66,308 UK Biobank participants under 50, free of cancer at baseline.
• Evaluated sex-specific polygenic risk scores (PRS) for total and breast cancer, alongside health-associated lifestyle scores (HLS) encompassing smoking, BMI, physical activity, alcohol, and diet.
• Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for early-onset total and breast cancer incidence.

Key Points:

• Higher genetic risk (highest PRS tertile) was significantly associated with increased risks of early-onset total cancer in both females (HR: 1.85) and males (HR: 1.94), and early-onset breast cancer in females (HR: 3.06).
• An unfavorable lifestyle (highest HLS category) was linked to higher total and breast cancer risk in females, with a stronger association observed in the highest genetic risk category.
• Genetic and lifestyle factors demonstrated independent associations with early-onset cancer risk.

Conclusions:

• Both genetic susceptibility and lifestyle choices are independently associated with the risk of developing early-onset total and breast cancer.
• Individuals with a high genetic predisposition may experience greater protective benefits from adopting a healthy lifestyle to mitigate early-onset cancer risk.