Associations of combined lifestyle and genetic risk with incident head and neck cancer: a prospective study in the UK Biobank

To investigate the relationship between genetic risk and the four main lifestyle factors in HNC development, we used data from 356,627 participants in the UK Biobank. Genetic risk was measured using a polygenic risk score (PRS), calculated as a weighted sum of risk alleles from four validated SNPs in previous GWAS. Participants were grouped into low, intermediate, and high genetic risk. Lifestyle scores(smoking, alcohol, activity, diet) were categorized as favorable, intermediate, or unfavorable. Over a median follow-up of 9.3 years, 658 incident HNC cases were identified. Cumulative incidence was 0.14% for low, 0.16% for intermediate, and 0.21% for high group. Compared with participants with an unfavorable lifestyle, those with a favorable lifestyle had significantly lower risk (HR: 0.30; P < 0.001), as did those with an intermediate lifestyle (HR: 0.43; P < 0.001). Among high genetic-risk individuals, cumulative incidence was 0.15% for those with favorable lifestyles versus 0.63% for those with unfavorable lifestyles (HR: 0.27; P < 0.001). Among low genetic-risk individuals, cumulative incidence was 0.11% for those with favorable lifestyles versus 0.44% for those with unfavorable lifestyles (HR: 0.29; P < 0.001). These findings suggest unhealthy lifestyles substantially increase HNC risk. Genetic risk and lifestyle are both associated with HNC risk. Healthy lifestyles can substantially lower HNC risk, even among high genetically susceptible individuals. Our findings emphasize the potential of lifestyle interventions in cancer prevention, regardless of genetic predisposition.