||1R01CA242558-01 Interpret this number
||Ut Southwestern Medical Center
||Early Life Exposures and Risk of Young-Onset Colorectal Cancer
In contrast to dramatic declines in older populations, the incidence of colorectal cancer (CRC) has nearly
doubled among younger adults since the early 1990s. Mechanisms contributing to the rising incidence of
young‐onset CRC (age <50 years) have puzzled researchers for years, and to date, family history of polyps or
CRC remains the only clearly established risk factor. Our prior work shows a strong birth cohort effect,
whereby incidence increased markedly among persons born in or after the 1960s. Higher incidence of young‐
onset CRC among this birth cohort (approximately Generation X) implicates environmental exposures in early
life. Antibiotics, cesarean delivery, birth weight, and childhood obesity – increasingly prevalent in early life –
may contribute to rising incidence of young‐onset CRC. Prevalence of these environmental exposures
exploded among persons born after 1960. For example, broad‐spectrum antibiotic use nearly tripled among
children of the 1960s, and cesarean deliveries increased from 5% of births in 1960 to more than 30% in 2015.
Mounting evidence suggests these environmental exposures alter gut microbiota, and gut microbiota may act
as a key promoter of carcinogenesis, thus, mediating the relationship of environmental exposures with CRC. In
the proposed project, we will generate timely evidence concerning effects of environmental exposures in early
life on risk of young‐onset CRC and advance our understanding of causal mechanisms contributing to this
disease. We will leverage existing data on 19,044 children enrolled in the Child Health and Development
Studies (CHDS), and for whom we can ascertain young‐onset CRC diagnoses with high‐quality cancer registry
data. CHDS comprises a diverse, population‐based cohort of children born in the 1960s to women receiving
prenatal care in the Kaiser Foundation Health Plan (Oakland, California). CHDS collected information on
prenatal visits, labor and delivery, and pediatric visits. These data do no rely on parents' or study participants'
memory but excellent capture of individual‐level risk factors collected prospectively from medical records. We
will append these well‐characterized data with information on family history and germline mutations by re‐
contacting CHDS participants for consent to obtain biospecimens. Our innovative use of data from an existing
cohort study, combined with genomic data collected in the present day, will provide a more complete picture
of young‐onset CRC than has been previously possible. We will: 1) Estimate the association of antibiotics
(prenatal, perinatal, childhood), cesarean delivery, birth weight, and childhood obesity and young‐onset CRC;
2) Explore whether the association between these early life exposures and young‐onset CRC differs among
those with and without a family history and/or germline mutation; and 3) Estimate the population impact of
early life exposures on risk of young‐onset CRC, by synthesizing effect estimates with prevalence of early life
exposures derived from population‐based surveys. By leveraging data on early life exposures from CHDS, we
will generate new evidence that may ultimately be applied to CRC prevention and risk‐reduction strategies.
Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults.
, Murphy C.C.
Gastroenterology, 2020 01; 158(2), p. 341-353.