Pack-Years as a Stable Predictor of Cancer Incidence and Mortality: A Prospective Cohort Study from the UK Biobank

Background To clarify the dose-response relationship between cigarette smoking and the risk of developing or dying from multiple site-specific cancers. Methods We prospectively analyzed baseline smoking pack-years in relation to cancer incidence and mortality in the UK Biobank, with data obtained from national cancer registries. Using a competing risk model, we assessed the associations between smoking pack-years and cancer outcomes, adjusting for age, gender, ethnicity, BMI, SES, drinking habits, and family cancer history. Results The study involved 336,885 individuals with a mean age of 55.9 years (SD 8.07), 53% of whom were female. There were 33,099 (9.8%) current smokers with an average of 27.16 (SD 18.38) pack-years and 87,241 (25.9%) former smokers with an average of 21.36 (SD 18.24) pack-years. Over a median follow-up of 13.93 years, 36,964 cancer events and 11,931 cancer deaths were recorded. The incidence and mortality risks of overall cancers increased linearly with smoking pack-years. Each additional pack-year increased the risk of all cancers by 0.9% (HR = 1.009, 95% CI = 1.008–1.009) and smoking-related cancers by 1.7% (HR = 1.017, 95% CI = 1.017–1.018). Cancer mortality rose by 1.5% per pack-year (HR = 1.015, 95% CI = 1.015–1.016), particularly in lung, bladder, esophageal, liver, and stomach cancers, with HRs ranging from 1.010 to 1.028. The study highlights the linear relationship between smoking pack-years and cancer risk, especially for smoking-related cancers. However, some cancers showed no significant correlation or an opposite effect. Conclusion Pack-years of smoking provide a linear representation of smoking’s impact on cancer incidence and mortality, significantly affecting various malignancies, particularly smoking-related ones.