The purpose of this Notice of Special Interest (NOSI) is to stimulate research focused on the roles of early-life factors (maternal-paternal, in utero, birth and infancy, puberty, adolescence, and young adult years) in cancer development later in life.
Given that current emerging evidence from limited research indicates a potentially important role for early-life events and exposures in cancer development, it is necessary to better understand:
1) The early-life factors that are associated with later cancer development;
2) How early-life factors mediate biological processes relevant to carcinogenesis; and
3) Whether predictive markers for cancer risk based on what happens at early life can be measured and developed for use in cancer prevention strategies. Markers that predict malignancy or pre-malignant conditions would allow assessment of early-life exposures with relevant outcomes without having to wait decades for cancer development.
Ultimately, a better understanding of early-life events and exposures, and the risk for cancer later in life may lead to the development of effective interventions as early as during pregnancy or starting early in the life course that may have a profound impact on cancer prevention.
Most of the epidemiology research conducted to date has focused on cancer risk factors in adulthood, but it is becoming increasingly evident that early-life factors have important consequences for cancer development later in life. For example, prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen prescribed for miscarriage prevention, increased risk for cancers of the cervix, vagina, and breast in the daughters of the women who received DES. Other evidence shows that early menarche is an established risk factor for breast cancer, an observation which sparked interest in the possibility that this early time-period is critical in the etiology of this disease. Early-life infections, likely in combination with immunogenic factors, have been associated with several adult malignancies. Infections by human papilloma viruses (HPV), which are usually acquired during teenage and young adult years, cause almost all invasive cervical cancer cases worldwide following a decades-long process. A single acute exposure to radiation to those who were in utero or in early childhood at the time of the atomic bombings of Hiroshima and Nagasaki resulted in significantly elevated risk of malignancies decades later. However, many unanswered questions remain. Size at birth (i.e., birth weight and length) also is associated with breast cancer risk. Birth size, a possible proxy for the prenatal environment and growth, has not adequately been studied for cancer outcomes. In addition to early growth, having been breast fed, exposures around the time of puberty, and other factors warrant further exploration. Whether DES-exposed sons have increased risks of testicular or prostate cancer is also unclear and further research is needed.
Research on early-life factors and cancer development has occurred almost exclusively in European American populations and, therefore, there is also an interest in understudied and underserved populations. Innovative approaches and designs can be used to address research questions by leveraging existing data and biospecimen resources. For example, researchers could access the Childhood Cancer Data Initiative (CCDI) by linking to the National Childhood Cancer Registry (NCCR) for cases for case-control studies.
This NOSI seeks to further support research on early-life factors and cancer development later in life.
Studies proposed in response to this NOSI should focus on human studies, but may incorporate research using animal models, especially in elucidating mechanisms relevant in humans. Human studies can be new, but applicants are encouraged to take advantage of existing resources such as from case-control and prospective studies, including birth cohort studies, and existing databases to utilize data and biological specimens to test hypotheses.
NCI recognizes the needs to support research focused on early-life factors and cancer development in humans because this is an area of research that remains highly understudied, but has the potential to be transformative in terms of cancer prevention and intervention strategies, earlier in life as opposed to the current practice.