Earlier age at menarche and breast development is associated with an increased risk of breast cancer. The average age at menarche has been declining in the U.S. and globally, and national studies show even more dramatic declines in the age of breast development (as defined by Tanner stage T2 or higher); a greater proportion of U.S. girls are beginning T2+ at ages 7-8. Early pubertal development results in longer lifelong exposure to sex steroids (i.e. estrogen and progesterone). Sex-steroids promote mammary cell proliferation, which increases susceptibility to environmental exposures that could initiate carcinogenesis. Larger childhood body size is one major explanation for the declines in pubertal development. However, even in cultures with much lower childhood obesity (e.g., Hong Kong), there is evidence that pubertal timing is also declining suggesting that other factors are at play. One major ecological change has been the decline in childhood infections from public health measures that have resulted in reduced exposure and increased resistance to infectious agents. Emerging lines of evidence, though limited, suggests that early infancy and childhood infections may be associated with delayed pubertal timing. Infection may not allow the body to spend energy in pubertal development at the expense of the immune system, down-regulating steroid hormone production and/or receptors; therefore, resulting in later pubertal timing and a decrease in breast cancer risk. While the majority of literature focuses on childhood obesity, there is an urgent need to understand other factors that may contribute to pubertal timing, such as childhood infections. There are few cohorts in the world however that are available to address specific hypotheses about childhood infections and pubertal timing. Using LEGACY (R01CA138822), a prospective study enriched with girls with a breast cancer family history (recruited ages 6- 13 years, N=1,040) designed to study childhood exposures and pubertal development, I will address the understudied etiological pathway of infection and puberty. My training in infectious disease epidemiology, behavioral oncology, and cancer epidemiology make me uniquely qualified to examine the association between puberty (i.e. age of onset of breast development and menarche) and: 1) childhood serologic infection burden of prevalent infections (EBV, CMV, HSV1/2 32-68% national seroprevalence) and 2) childhood infection burden (as measured by mother reported infectious exposures and medical records) across 5 time periods (0-12 months, age (years) 1-5 , 6-10, 11-13, 14-18). Specifically, by building efficiently on one of the largest studies in the world of girls' puberty and coupling my novel research questions with additional training in molecular epidemiology, family-based studies, infection and health, pubertal development, and longitudinal modeling, I will be able to also examine molecular changes related to infections and relevant to pubertal timing that are a part of the hormonal and immunoregulatory pathways. This study will provide essential evidence for the role of exposures to childhood infection and pubertal timing, dependent or independent of adiposity.
The incidence of invasive breast cancer in women under the age of 40 years has increased and earlier age at breast development and age at menarche are key breast cancer risk factors that have changed over this time period that may help explain these changes. While the increase in childhood body size can explain some of the decline in pubertal timing, earlier puberty in populations with very low childhood obesity still see earlier ages at puberty; changes in childhood infectious exposures may play a role in pubertal timing in girls. Focusing on early life factors that contribute to the declining age of puberty are important for understanding the long lasting impact on breast cancer risk, especially for individuals with and without a breast cancer family history.
| McDonald, Jasmine A; Tehranifar, Parisa; Flom, Julie D et al. (2018) Hair product use, age at menarche and mammographic breast density in multiethnic urban women. Environ Health 17:1 |
| Zeinomar, Nur; Thai, Ashley; Cloud, Ann J et al. (2017) Alcohol consumption and breast cancer-specific and all-cause mortality in women diagnosed with breast cancer at the New York site of the Breast Cancer Family Registry. PLoS One 12:e0189118 |
| McDonald, J A; Eng, S M; Dina, O O et al. (2016) Infection and pubertal timing: a systematic review. J Dev Orig Health Dis 7:636-651 |
