Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study
Year: 2023
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk. METHODS: We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants. RESULTS: Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05). CONCLUSIONS: Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.
Source: BMC Medicine
Authors: Nikos Papadimitriou, Caroline J Bull, Mazda Jenab, David J. Hughes, Joshua A Bell, Eleanor Sanderson, Nicholas J Timpson, George Davey Smith, Demetrius Albanes, Peter T Campbell, Sébastien Küry, Loic Le Marchand, Cornelia M Ulrich, Kala Visvanathan, Jane C Figueiredo, Polly A Newcomb, Rish K Pai, Ulrike Peters, Kostas K Tsilidis, Jolanda M.A. Boer, Emma E Vincent, Daniela Mariosa, Marc J Gunter, Tom G Richardson, Neil Murphy
Institutions: Centre international de recherche sur le cancer, University of Bristol, MRC Integrative Epidemiology Unit, University College Dublin, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, American Cancer Society, Albert Einstein College of Medicine, Centre Hospitalier Universitaire de Nantes, Nantes Université, University of Hawaii Cancer Center, University of Utah, Huntsman Cancer Institute, Johns Hopkins University, Cedars-Sinai Medical Center, Fred Hutch Cancer Center, Mayo Clinic in Arizona, University of Washington, University of Ioannina, Imperial College London, National Institute for Public Health and the Environment, Novo Nordisk (United Kingdom)
Language: English
Topic: Cancer Risks and Factors
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: World Health Organization, Centre International de Recherche sur le Cancer, Wellcome Trust, World Cancer Research Fund International, UK Research and Innovation, Cancer Research UK, National Institute for Health and Care Research, Diabetes UK, University of Bristol, Novo Nordisk, Medical Research Council, World Cancer Research Fund, National Cancer Institute
Awards: G1131969086, G1684393010, G173885373, G1793884970, G1987169411, G2203228061, G235045266, G2466259667, G2538597952, G2642749895, G303234583, The influence of cancer on people with Type 2 diabetes, G323433674, G324601231, G3264092773, G3288322216, G3344456887, G3507283293, G3609641447, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3734181317, G3987754321, G4603568690, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G5329469444, G5371351582, Dissecting the molecular aetiology of complex traits using high dimensional omic data, G5788305929, G5850737185, G6223152210, G6384266951, G6423108142, G6682065591, Mendelian randomization to hypothesis-free causal inference, G7157845406, G7283805961, G7698318594, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being., G7990456425, G8201869620, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G8502142660, G8530269906, G8930023330, G896001452, University of Hawaii Cancer Center CCSG
OpenAlex ID: W4313546307