Identifying Opportunities for Cancer Prevention During Preadolescence and Adolescence: Puberty as a Window of Susceptibility

Division of Adolescent Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: .
Journal of Adolescent Health (Impact Factor: 3.61). 05/2013; 52(5 Suppl):S15-20. DOI: 10.1016/j.jadohealth.2012.09.019
Source: PubMed


Early life exposures during times of rapid growth and development are recognized increasingly to impact later life. Epidemiologic studies document an association between exposures at critical windows of susceptibility with outcomes as diverse as childhood and adult obesity, timing of menarche, and risk for hypertension or breast cancer.
This article briefly reviews the concept of windows of susceptibility for providers who care for adolescent patients.
The theoretical bases for windows of susceptibility is examined, evaluating the relationship between pubertal change and breast cancer as a paradigm, and reviewing the underlying mechanisms, such as epigenetic modification.
The long-term sequela of responses to early exposures may impact other adult morbidities; addressing these exposures represents an important challenge for contemporary medicine.

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Available from: Frank Biro, Feb 19, 2014
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    • "This observation suggests further investigation on the role of n-3 PUFA in regulating hormonal influences on puberty and cancer. Furthermore, this observation supports growing evidence that critical periods of early development such as puberty have important influences on future cancer risk [23,30,31]. "
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    ABSTRACT: Background Breast cancer is attributable to modifiable risk factors including the intake of dietary n-3 polyunsaturated fatty acids (PUFA). A key piece of evidence, yet to be addressed, that would demonstrate a causal relationship between n-3 PUFA and breast cancer, is a dose-dependent effect of n-3 PUFA on tumour outcomes. Thus, the objective of the present study was to determine whether n-3 PUFA reduces mammary gland tumor outcomes in a dose-dependent manner in female MMTV-neu(ndl)-YD5 transgenic mice, an aggressive model of human breast cancer. Methods Harems were provided one of three experimental diets comprised of 0, 3 or 9% (w/w) menhaden fish oil containing n-3 PUFA. Female offspring were weaned onto the same parental diet and maintained on their respective diet for 20 weeks. Tumour onset, size and multiplicity were measured throughout the study. Fatty acid composition of mammary gland and tumours were determined by gas–liquid chromatography. Results Tumour size was significantly (p < 0.05) reduced in a dose-dependent manner. n-3 PUFA were also incorporated in a dose-dependent manner; differential incorporation was observed for eicosapentaenoic and docosapentaenoic acids into mammary gland tissue, while docosahexaenoic acid was preferentially incorporated into tumours. Conclusion Overall, the present study provides fundamental knowledge about the dose-dependent effect of n-3 PUFA on tumour outcomes in a pre-clinical model and also sheds light on the differential role of individual n-3 PUFA on tumour outcomes.
    Lipids in Health and Disease 06/2014; 13(1):96. DOI:10.1186/1476-511X-13-96 · 2.22 Impact Factor
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    • "However, the specific mechanisms responsible for the protective effects of n-3 PUFA remain elusive. Emerging research suggests that timing of exposure is an important modifier of breast cancer risk (Biro and Deardorff 2013; MacLennan and Ma 2010). During puberty, the mammary gland undergoes extensive growth and development. "
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    ABSTRACT: There is growing evidence that early developmental periods may importantly influence future breast cancer risk. Also, there is great interest in the role of dietary fat in breast cancer risk, but the role of dietary fat during pubertal mammary gland development remains poorly understood. This study investigated the effect of n-3 polyunsaturated fatty acids (PUFA) using complementary dietary and genetic approaches to examine the effect of lifelong exposure of n-3 PUFA or n-6 PUFA (control) on mammary gland development and fatty acid composition. n-3 PUFA from both diet and genetics were enriched in mammary glands as early as 3 weeks of age. Parameters related to mammary gland development, including number of terminal end buds (TEB), percent coverage of ductal tree, and infiltration of TEB, were influenced by n-3 PUFA at 3 and 4 weeks of age. Overall, findings suggest that n-3 PUFA incorporation into the mammary gland early in life plays a role in the morphological development of the mammary gland during puberty.
    Applied Physiology Nutrition and Metabolism 03/2014; 39(6). DOI:10.1139/apnm-2013-0365 · 2.34 Impact Factor
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    • "However, a great reduction in life quality due to major side-effects of therapies is limiting the success of therapy (21–23). During early age organ development and maturation, the spectrum of mutations causing malignant transformations results in notable differences in the spectrum of cancers between children and adults (24, 25). Understanding the genetic abnormalities underlying adult and pediatric cancers is an essential step in developing novel drug therapies for cancers, and especially so for pediatric cancers. "
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    ABSTRACT: In genome science, the advancement in high-throughput sequencing technologies and bioinformatics analysis is facilitating the better understanding of Mendelian and complex trait inheritance. Charting the genetic basis of complex diseases - including pediatric cancer, and interpreting huge amount of next-generation sequencing data are among the major technical challenges to be overcome in order to understand the molecular basis of various diseases and genetic disorders. In this review, we provide insights into some major challenges currently hindering a better understanding of Mendelian and complex trait inheritance, and thus impeding medical benefits to patients.
    Frontiers in Pediatrics 03/2014; 2:12. DOI:10.3389/fped.2014.00012
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