Early life exposures and cancer in adulthood: World Cancer Research Fund International's lifecourse research in cancer

Background There is increasing recognition that exposure to certain risk factors in early life (defined as birth, childhood, adolescence, and young adulthood) impacts disease risk (including cancer) in adulthood. The identification of age-specific “windows of opportunity” also enables the development of refined cancer prevention recommendations tailored to different life stages. Despite this, there is a paucity of evidence related to how body size and weight, diet, nutrition, and physical activity in early life influences adult cancer risk. The strength of the available evidence-base has also not been assessed in a systematic way. Methods WCRF International's Global Cancer Update Programme (CUP Global) undertook a collaboration with Wageningen University and Research (WUR) to conduct systematic literature reviews and meta-analyses focused on early-life exposures (birth size, body weight, and alcohol consumption) and risk of colorectal and breast cancer in adulthood. A 2 nd collaboration with the International Agency for Research on Cancer (IARC) reviewed relevant biological mechanisms. The Global CUP Global Panel of Experts then interpreted and graded the evidence using pre-defined criteria to determine likely causal associations. Results Key exposures during early life related to birthweight, body size and alcohol, as well as the biological mechanisms that underpin them, that impact future cancer risk were identified. For colorectal cancer, birthweight was associated with a 9% (95% confidence interval: 1.01-1.16) increased risk, increased BMI during childhood, adolescence and young adulthood were also associated with increased risk. For breast cancer, greater birth weight, length and taller height in childhood inferred an increased risk. Higher BMI in childhood, adolescence and young adulthood were associated with lower risk. Our Panel of Experts concluded that the evidence for several of the associations was strong enough to suggest a likely causal association. In the future, WCRF International will use these results and further discussions with experts in the field of lifecourse research, public health, and policy to develop guidance and recommendations for researchers, policy makers and the public. Conclusion The current reviews of the epidemiological and mechanistic evidence demonstrate how exposures related to diet, nutrition, and bodyweight can impact cancer risk in adulthood. Understanding the associations between our early years and cancer risk in adulthood enables a better understanding of the aetiology of cancer, how risk factors impact cancer risk as we age, whether there are critical timepoints/windows for cancer risk, and how our environment impacts cancer risk. These findings, alongside a growing evidence-base, enable the development of cancer prevention policy and public health recommendations.