Healthy lifestyle, genetic risk, and incidence of cancer: A prospective cohort study of 13 cancer types

Background Genetic and lifestyle factors are related to the risk of cancer, but it is unclear whether a healthy lifestyle can offset genetic risk. Our aim was to investigate this for 13 cancer types using data from the UK Biobank prospective cohort. Methods In 2006-2010, participants aged 37-73 years were assessed and followed until 2015-2019. Analyses were restricted to those of European ancestries with no history of malignant cancer (n=195,822). Polygenic risk scores (PRSs) were computed for 13 cancer types and these cancers combined (‘overall cancer’), and a healthy lifestyle score was calculated from current recommendations. Relationships with cancer incidence were examined using Cox regression, adjusting for relevant confounders. Interactions between HLI and PRSs were assessed. Results There were 15,240 incident cancers during the 1,926,987 person-years of follow-up (median follow-up= 10.2 years). After adjusting for confounders, an unhealthy lifestyle was associated with a higher risk of overall cancer [lowest vs highest tertile hazard ratio (95% confidence interval) = 1.32(1.26, 1.37)] and eight cancer types. The greatest increased risks were seen for cancers of the lung [3.5(2.96,4.15)], bladder [2.03 (1.57, 2.64)], and pancreas [1.98 (1.54,2.55)]. Positive additive interactions were observed, suggesting a healthy lifestyle may partially offset genetic risk of colorectal, breast, and pancreatic cancers, and may completely offset genetic risk of lung and bladder cancers. Conclusions A healthy lifestyle is beneficial for most cancers and may offset genetic risk of some cancers. These findings have important implications for those genetically predisposed to these cancers and population strategies for cancer prevention.