Early-Life Exposures and Adult Cancer Risk: A Life Course Approach to Cancer Prevention
Clarke, Megan A.
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Background Despite emerging evidence indicating the potential importance of early-life exposures for adult cancer risk, there is limited research investigating cancer risk factors in early-life. The goals of this dissertation are to 1) elucidate whether maternal adiposity influences epigenetic processes in the offspring relevant to obesity and carcinogenesis and 2) inform primary cancer prevention strategies by addressing two modifiable, early-life risk factors: human papillomavirus (HPV) in males and unhealthy diet in postpartum teens. Methods Study 1: We evaluated the association of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with umbilical cord blood DNA methylation in a prospective study of 112 black and white mothers and infants, enrolled in Baltimore, MD, 2006-2007. Study 2: We identified predictors of HPV vaccination using electronic medical record data from 14,688 males aged 11-26 years in Maryland, 2012-2013. Study 3: We examined associations of perceived school and home food environments with dietary behaviors using baseline data from 853 postpartum teens enrolled in a weight-loss intervention study across 27 states, 2007-2009. Questionnaire items measuring perceived access to healthful items were used to categorize environments as “positive” or “negative”. Results Study 1: Maternal pre-pregnancy BMI and GWG were significantly associated with DNA methylation in several CpG sites within 17 candidate genes. A majority of these associations were sex-specific. Study 2: Approximately 15% of males initiated the HPV vaccine. Non-Hispanic black males (vs. non-Hispanic white) and publicly insured males (vs. private), were more likely to initiate the HPV vaccine, but less likely to receive subsequent doses. Frequent clinic visits (>3) were associated with increased uptake of all three doses. Study 3: A positive school environment was related to healthful eating behaviors such as fruit consumption. In contrast, a positive home environment was associated with frequent consumption of a wider variety of healthful items as well as infrequent consumption of unhealthful food and beverages. Conclusion Early-life is an important, yet understudied period with respect to cancer risk. A better understanding of early-life factors from both an etiologic and primary prevention perspective will help to inform interventions that may substantially impact current cancer prevention strategies.