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. 2023 Jun 6;52(3):817-826.
doi: 10.1093/ije/dyac238.

Lifestyle, genetic risk and incidence of cancer: a prospective cohort study of 13 cancer types

Stephanie Byrne  1   2   3 , Terry Boyle  1   2   3 , Muktar Ahmed  1   3   4   5 , Sang Hong Lee  1   2   3 , Beben Benyamin  1   2   3 , Elina Hyppönen  1   3   4
Affiliations

Lifestyle, genetic risk and incidence of cancer: a prospective cohort study of 13 cancer types

Stephanie Byrne et al. Int J Epidemiol. .

Abstract

Background: Genetic and lifestyle factors are associated with cancer risk. We investigated the benefits of adhering to lifestyle advice by the World Cancer Research Fund (WCRF) with the risk of 13 types of cancer and whether these associations differ according to genetic risk using data from the UK Biobank.

Methods: In 2006-2010, participants aged 37-73 years had their lifestyle assessed and were followed up for incident cancers until 2015-2019. Analyses were restricted to those of White European ancestry with no prior 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 lifestyle index was calculated from WCRF recommendations. Associations with cancer incidence were estimated using Cox regression, adjusting for relevant confounders. Additive and multiplicative interactions between lifestyle index 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, the lifestyle index was associated with a lower risk of overall cancer [hazard ratio per standard deviation increase (95% CI) = 0.89 (0.87, 0.90)] and of eight specific cancer types. There was no evidence of interactions on the multiplicative scale. There was evidence of additive interactions in risks for colorectal, breast, pancreatic, lung and bladder cancers, such that the recommended lifestyle was associated with greater change in absolute risk for persons at higher genetic risk (P < 0.0003 for all).

Conclusions: The recommended lifestyle has beneficial associations with most cancers. In terms of absolute risk, the protective association is greater for higher genetic risk groups for some cancers. These findings have important implications for persons most genetically predisposed to those cancers and for targeted strategies for cancer prevention.

Keywords: Cancer; alcohol consumption; diet; genetic risk; lifestyle; obesity; physical activity; smoking.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
Ascertainment of the study sample included in the analyses
Figure 2
Figure 2
Adjusted associations between the lifestyle index, polygenic risk score and cancer. Cox proportional hazards regression adjusted for age at baseline, sex (where relevant), assessment centre, 40 principal components of ancestries, Townsend Index, education, birth location and income; overall cancer = overall incident cases of the 13 cancer types assessed in this study
Figure 3
Figure 3
Risk of colorectal, post-menopausal breast, lung, pancreatic and bladder cancers according to genetic risk and lifestyle. Cox proportional hazards regression adjusted for age at baseline, sex (where relevant), assessment centre, 40 principal components of ancestries, Townsend Index, education, birth location and income; LI, lifestyle index; pyar, person-years at risk; HR, hazard ratio
See this image and copyright information in PMC

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