Body mass index at birth and early life and colorectal cancer: A two‐sample Mendelian randomization analysis in European and East Asian genetic similarity populations

• Published in: Pediatric obesity Vol. 20; no. 1; pp. e13186 - n/a
• Main Authors: Papadimitriou, Nikos, Murphy, Neil, Jenab, Mazda, Chen, Zhishan, Brenner, Hermann, Kweon, Sun‐Seog, Le Marchand, Loic, Moreno, Victor, Platz, Elizabeth A., Duijnhoven, Fränzel J. B., Cheng, Iona, Pai, Rish K., Phipps, Amanda I., Peters, Ulrike, Zheng, Wei, Hughes, David J.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Inc 01.01.2025
• Subjects: Adult; Asia, Eastern - epidemiology; Body Mass Index; Child; Child, Preschool; colorectal cancer; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; early life; East Asian People - genetics; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Infant; Infant, Newborn; Male; mendelian randomization; Mendelian Randomization Analysis; Norway - epidemiology; obesity; Polymorphism, Single Nucleotide; Risk Factors; White People - genetics; Asia, Eastern; Norway; colorectal cancer; mendelian randomization; obesity; early life
• ISSN: 2047-6302; 2047-6310
• DOI: 10.1111/ijpo.13186

Summary Background Varying obesogenic inherited predisposition in early to later life may differentially impact colorectal cancer (CRC) development. Previous Mendelian randomization (MR) studies, conducted in populations of European genetic similarity, have not observed any significant associations between early life body weight with CRC risk. However, it remains unclear whether body mass index (BMI) at different early lifetime points is causally related with CRC risk in both Europeans and East Asian populations. Objectives We conducted a two‐sample MR study to investigate potential causal relationships between genetically predicted BMI during early life (birth to 8 years old) and at specific periods (birth, transient, early rise and late rise) and CRC risk. Methods Summary data were obtained from genome‐wide association study (GWAS) of BMI in 28 681 children from the Norwegian Mother, Father and Child Cohort Study (MoBa) study and applied to CRC GWAS data from European and East Asian descent populations (102 893 cases and 485 083 non‐cases). Results There were no significant associations observed between early life BMI and CRC risk in European or East Asian populations. The effect estimates were similar in European studies (odds ratio [OR] per a 1‐standard deviation [SD] increase: 1.01, 95% confidence interval [CI]: 0.95, 1.07) and in East Asians (OR per a 1‐SD increase: 1.02, 95% CI: 0.91, 1.14). Similar nonsignificant associations were found between time of BMI measurement during childhood and cancer‐site‐specific analyses. Conclusions We found little evidence of any associations between early life adiposity on later life CRC risk.