Background: Many lifestyle factors are known to affect cancer risk, and these association may vary depending on individuals’ cardiometabolic genetic risk and socioeconomic environment. However, less is understood about the combined effects of lifestyle factors and their interaction with genetic predisposition to cardiometabolic diseases and socioeconomic position.
Objectives: This study examined whether associations between lifestyle factors and lifestyle-related cancer risk vary by genetic predisposition to cardiometabolic diseases and by socioeconomic position.
Methods: We used data from UK Biobank (UKB), a prospective cohort of 501,939 adults aged 40-69 recruited between 2006 and 2010. We created a healthy lifestyle index (HLI) based on diet, physical activity (MET-hours/week), sedentary behaviour (hours/day), Body mass index (BMI) (kg/m²), alcohol (gram/day), smoking status, and sleep quality. Polygenic risk score of cardiovascular disease, type 2 diabetes, and BMI were obtained from the standard polygenic risk score resource available in UKB. Socioeconomic position score was created using education, income, and the Townsend deprivation index. We defined lifestyle-related cancers as those linked to at least four of the lifestyle factors, including colorectal, breast (post-menopause), pancreas, liver, oesophageal, stomach (cardia), lung, mouth (without salivary gland), pharynx, and larynx cancers. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HLI and lifestyle-related cancer risk by cardiometabolic diseases polygenic risk score and socioeconomic position. Additive interaction was quantified by relative excess risk due to interaction (RERI).
Results: During a median follow-up of 11 years (range: 6.8 – 11.8), 21,717 first primary lifestyle-related cancers were recorded. Each 1-standard deviation (SD) increased in HLI score was associated with a 19% (CI: 21% to 17%) lower lifestyle-related cancer risk. Across genetic risk strata, higher HLI remained protective. Individuals with lower cardiovascular disease, type 2 diabetes, and BMI polygenic risk score had a 20% (CI: 24% to 16%), 22% (CI: 26% to 17%) and 21% (CI: 25% to 16%) lower risk, respectively, per 1-SD increase in HLI score. While those with higher polygenic risk score had a 18% (CI: 22% to 13%), 17% (CI: 22% to 13%) and 17% (CI: 21% to 12%) lower risk, respectively. No evidence of an additive interaction between HLI and any of cardiometabolic disease polygenic risk score was observed. In contrast, A significant positive additive interaction observed between HLI and socioeconomic position (RERI= 0.23, CI: 0.11 to 0.35, P< 2e-16). Individuals with both low HLI and low socioeconomic position had a 63% higher lifestyle-related cancer risk (CI:46% to 83%) compared with those with high HLI and high socioeconomic position.
Conclusions/Implications for practice or policy: Maintaining a healthy lifestyle is associated to reduced lifestyle-related cancer risk across all cardiometabolic diseases polygenic risk score and socioeconomic position groups. While individuals with lower genetic risk saw slightly greater benefits, socioeconomic position clearly modified the association that emphasize addressing social inequalities is essential to maximize the effectiveness of HLI.