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It examines sex-specific patterns in metabolism, immunity, pluripotency, and tumor suppressor functions, integrating imprinting, sex chromosome complement, X-inactivation escape genes, sex hormones, and life-history timing. The discussion also considers age-dependent and behavior/exposure-related contributors to incidence, progression, and survival.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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on regarding cancer and sex differences?","Question",{"text":63,"@type":64},"It reviews how epigenetic mechanisms involved in sexual differentiation affect cancer hallmark pathways across life, emphasizing functions such as metabolism, immunity, pluripotency, and tumor suppression.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Why are sex differences in cancer described as both biological and contextual?",{"text":68,"@type":64},"Sex differences reflect interactions among imprinting, chromosomal and hormonal sex, developmental and life-history effects on epigenetics, plus measurable contributions from behaviors, exposures, and access to medical care.",{"name":70,"@type":61,"acceptedAnswer":71},"How does genomic imprinting relate to sex-specific cancer risk?",{"text":72,"@type":64},"Genomic imprinting mediates transgenerational transmission of epigenetic adaptations via differential DNA methylation in egg and sperm, which can be reprogrammed in XX- versus XY-biased ways to tailor 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Editor: Barbara Stranger  \nEpigenetic developmental mechanisms underlying sex differences in cancer  \nJoshua B. Rubin,1,2 Tamara Abou-Antoun,1 Joseph E. Ippolito,3,4 Lorida Llaci,5 Camryn T. Marquez,4 Jason P. Wong,1 and Lihua Yang1  \n1Department of Pediatrics, 2Department of Neuroscience, 3Department of Radiology, 4Department of Biochemistry and Molecular Biophysics, 5Deartment of Genetics Washington University School of Medicine, St. Louis, Missouri, USA.  \nCancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, we review the epigenetics of sexual differentiation and its effect on cancer hallmark pathways throughout life. Specifically, we will touch on how sex differences in metabolism, immunity, pluripotency, and tumor suppressor functions are patterned through the epigenetic effects of imprinting, sex chromosome complement, Xinactivation, genes escaping X inactivation, sex hormones, and life history.  \nIn humans, cancer occurs more commonly in males, and males die more rapidly of their disease compared with females (1). When we observe significant sex differences such as these, they are the result of sexual differentiation, a continuous process from gametogenesis to death. Sex differences in cancer incidence and outcome arise through multiple mechanisms. First are interactions between imprinting, chromosomal and hormonal sex, and developmental and life history effects on epigenetics. Together, these produce significant sex differences in growth regulation, metabolism, immunity, longevity, cell cycle regulation, response to DNA damage, p53 and retinoblastoma protein (pRB) function, among other determinants of health and lifespan (1). Second are the measurable effects of behaviors, exposures, and access to medical care, which account for variable proportions of overall cancer risk (2) . These stressors and behaviors include those associated with gender expectations, roles, and identity. We will continue to refer to the differences we are discussing as sex differences, while recognizing that sex cannot be fully disentangled from gender, which also plays an important role in cancer risk.  \nSex differences are individualized and vary in magnitude asa function of age. Thus, there is no complete dichotomy between being male or female. Despite this, it has proven productive to aggregate measured traits around male and female poles (3) . While not complete or wholly accurate, categorical sex contains a lot of information about sex effects on the range of human phenotypes in health and disease. In this Review, we will use  \nConflict of interest: The authors have declared that no conflict of interest exists. Copyright: © 2024, Rubin et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.  \nReference information: J Clin Invest. 2024;134(13):e180071 .  \n[https://doi.org/10.1172/JCI180071](https://doi.org/10.1172/JCI180071) .  \ncategorical terms based on sex chromosome complement to reveal a spectrum of sex-related phenotypes, while acknowledging their limitations.  \nCancer risk is determined by interactions between inherited genetics, somatic mutations, epigenetics, exposures, and age. Familial and sporadic retinoblastoma (RB) proved the point. In 1971 Knudson made careful observations about ","cbCaiupUL2M0hvm1","https://ap.wps.com/l/cbCaiupUL2M0hvm1","pdf",917809,12,"English","# Epigenetic developmental mechanisms and sex differences in cancer\n## Sex and gender as contextual determinants of cancer risk\n## Epigenetics across the life course\n## Genomic imprinting and transgenerational epigenetic transmission\n## Imprinted gene regulation and epigenetic mark establishment","[{\"question\":\"What does the review focus on regarding cancer and sex differences?\",\"answer\":\"It reviews how epigenetic mechanisms involved in sexual differentiation affect cancer hallmark pathways across life, emphasizing functions such as metabolism, immunity, pluripotency, and tumor suppression.\"},{\"question\":\"Why are sex differences in cancer described as both biological and contextual?\",\"answer\":\"Sex differences reflect interactions among imprinting, chromosomal and hormonal sex, developmental and life-history effects on epigenetics, plus measurable contributions from behaviors, exposures, and access to medical care.\"},{\"question\":\"How does genomic imprinting relate to sex-specific cancer risk?\",\"answer\":\"Genomic imprinting mediates transgenerational transmission of epigenetic adaptations via differential DNA methylation in egg and sperm, which can be reprogrammed in XX- versus XY-biased ways to tailor the future epigenome for each sex.\"}]","Epigenetic developmental mechanisms underlying sex differences in cancer | PDF",1789990667]