Background: It has been estimated that approximately 40% of new cancer cases every year are related to modifiable lifestyle factors, including smoking habits, alcohol intake, and obesity. Typically, the role of lifestyle factors on cancer incidence is investigated focussing on one variable(s) at the time, de facto ignoring potential synergistic relationships among behaviours (e.g. smoking and alcohol). As a result, the impact of modifiable factors is often evaluated addressing individual exposures separately, mostly using measures of relative risk.
Objectives: The aim of this study is to estimate absolute risks of developing specific cancers in relation to modifiable lifestyle factors, while accounting for the combined effects of multiple behaviours.
Methods: Leveraging data from the European Prospective Investigation into Cancer and nutrition (EPIC) and the UK Biobank, we will estimate cumulative incidence functions (CIF) to develop upper aerodigestive tract (UADT), breast, colorectal cancers, and hepatocellular carcinoma for combinations of alcohol intake, smoking, and obesity. All-cause mortality and incidence of non-UADT cancers will be treated as competing events in competing-risks analyses. CIF estimates will be computed overall, by sex, and socio-economic position.
Preliminary results: In a large pooled analysis of 28 international cohorts, the 15-year absolute risks to develop UADT cancers for a male participant aged 60 consuming between 30 and 60 g/day of alcohol were estimated to be 1.5% and 0.3%, in current and never smokers, respectively. For a female participant, the corresponding 15-year absolute risks were estimated to be 0.6% and 0.2%, in current and never smokers, respectively (Figure 1). These differences were driven by differential baseline UADT risks in never and current smokers. Alcohol consumption and smoking did not show a multiplicative interaction on the relative risk scale for UADT cancers.
Conclusions: Absolute risk estimation in competing risks analyses provides informative evidence on the impact of modifiable risk factors on cancer incidence. Rather than tackling individual risk factors in isolation, in this study we examined the combined role of multiple modifiable factors to support targeted prevention strategies that prioritise high-risk individuals.

Figure 1. Sex-specific estimates of cumulative incidence of UADT cancer for participants aged 60 at baseline over 15 years by categories of alcohol consumption and smoking status.