Adverse childhood experiences and cancer: A systematic review and meta-analysis.

Abstract

10565 Background: Cancer is one of the leading causes of morbidity and mortality globally, with increasing incidence rates. The major governing cancer societies identify cancer risk factors into five broad groups (infectious disease, environmental/chemical pollutants, genetics, behavioral and ultraviolet radiation). However, little attention has been dedicated to understanding the potential primordial risk of the early psychosocial environment. Life course epidemiology is a framework that considers how the harmful effects of adverse childhood experiences (ACEs) contribute to the development of disease later in life. It is postulated that such stressful events that occur during a critical period of development likely trigger increased inflammatory responses, which could ultimately contribute to the manifestation of chronic diseases such as cancer. While there are studies that have reported an association between ACEs and cancer, this relationship has yet to be systematically analyzed. The objectives of this study are to a) meta-analyze the pooled association of the presence of at least one ACE, b) the burden of different ACEs, and c) specific ACE types, and their association with cancer in adulthood. Methods: This systematic review compiled studies from PubMed, EMBASE, Medline, Web of Science, Google Scholar, Biological Psychiatry, and grey literature up to Mar 16, 2023, and was registered on PROSPERO. Observational studies with a comparator group that assessed ACEs that occurred prior to age 18, and diagnosed cancer ≥21 years of age were included. Two review authors independently screened articles, extracted data, assessed risk of bias using QUIPS, and conducted GRADE assessment. Pooled odds ratios (ORs) were calculated using multilevel linear random-effects models. Results: Of the total 39,658 articles, our search identified 26 studies, of which 23 studies (356,519 participants, 9 countries) were eligible for meta-analysis. The occurrence of ≥1 ACE(s) was associated with cancer (OR=1.16, 95% CI: 1.08-1.24, I2 = 58.7%), compared to participants with no ACEs. As the number of ACEs increased, the odds of cancer increased (≥4 ACEs compared to no ACEs OR=1.30, 1.04-1.62, p-trend = 0.0003). Specific ACE types did explain a significant amount of heterogeneity (F = 2.02, p = 0.04). Parental or sibling death (OR=1.88, 1.29-2.73), household mental illness (OR=1.36, 1.14-1.61), sexual abuse (OR=1.20, 1.04-1.37), and physical abuse (OR=1.18, 1.05-1.34) had the largest associations with cancer. Conclusions: Our findings confirm ACEs as important risk factors for cancer in adulthood. These findings have important clinical and public health implications to develop primary and secondary prevention and treatment strategies. Also, further research is warranted to explore this relationship on the epigenetic level, and among specific cancers.