Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Gender and sex interactions are intrinsic components of cancer phenotypes

Nature Reviews Cancer volume 25, pages 634–648 (2025)Cite this article

Subjects

Abstract

Sex is a significant determinant of cancer incidence and outcome. The effects of sexual differentiation on normal and cancer biology underly this epidemiology. The resultant sex differences in therapeutic target pathways and processes provide a foundation for developing more personalized cancer treatments. However, our efforts at personalization cannot stop there. Humans also have gender, and sex and gender are highly interactive in individuation. Thus, we will also need to consider how gender–sex interactions (GSI) affect cancer biology and clinical parameters such as the timing of diagnoses, clinical trial enrolment, and the completeness of efficacy and toxicity data. Ignoring the effects of GSI can compromise the quality of basic biological and clinical data and the conclusions drawn from them. This is not to say that GSI will always have a significant effect or any effect at all in every cancer study. Rather, it is to say that we know enough about GSI and human cancer to anticipate measurable differences when GSI are considered in research, enabling us to experimentally determine whether their effects are significant. Here, I delve deeply into GSI and cancer, as this approach to treatment personalization holds great promise to benefit all patients with cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: GSI and cancer risk.
Fig. 2: Sexual selection and resource allocation.
Fig. 3: Mouse models for studying chromosomal and gonadal effects on sexual differentiation.
Fig. 4: Conceptual model of GSI effects.

Similar content being viewed by others

References

  1. Ashley, D. J. A male-female differential in tumour incidence. Br. J. Cancer 23, 21–25 (1969).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Jackson, S. S. et al. Sex disparities in the incidence of 21 cancer types: quantification of the contribution of risk factors. Cancer 128, 3531–3540 (2022).

    Article  PubMed  Google Scholar 

  3. Goodenough, U. & Heitman, J. Origins of eukaryotic sexual reproduction. Cold Spring Harb. Perspect. Biol. 6, https://doi.org/10.1101/cshperspect.a016154 (2014).

  4. Hosken, D. J., Archer, C. R. & Mank, J. E. Sexual conflict. Curr. Biol. 29, R451–R455 (2019).

    Article  CAS  PubMed  Google Scholar 

  5. Cliquet, R. The relevance of sociobiological theory for emancipatory feminism. J. Hum. Evol. 13, 117–127 (1984).

    Article  Google Scholar 

  6. Rubin, J. B. The spectrum of sex differences in cancer. Trends Cancer 8, 303–315 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rubin, J. B. et al. Sex differences in cancer mechanisms. Biol. Sex Differ. 11, 17 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lonsdorf, E. V. et al. Sex differences in wild chimpanzee behavior emerge during infancy. PLoS One 9, e99099 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Nattrass, S. et al. Postreproductive killer whale grandmothers improve the survival of their grandoffspring. Proc. Natl Acad. Sci. USA 116, 26669–26673 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Seltmann, M. W., Helle, S., Htut, W. & Lahdenpera, M. Males have more aggressive and less sociable personalities than females in semi-captive Asian elephants. Sci. Rep. 9, 2668 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bouzy, J., Brunelle, J., Cohen, D. & Condat, A. Transidentities and autism spectrum disorder: a systematic review. Psychiatry Res. 323, 115176 (2023).

    Article  PubMed  Google Scholar 

  12. Cooper, K., Smith, L. G. E. & Russell, A. J. Gender identity in autism: sex differences in social affiliation with gender groups. J. Autism Dev. Disord. 48, 3995–4006 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mograbi, D. C., Rodrigues, R., Bienemann, B. & Huntley, J. Brain networks, neurotransmitters and psychedelics: towards a neurochemistry of self-awareness. Curr. Neurol. Neurosci. Rep. 24, 323–340 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Strang, J. F. et al. The autism spectrum among transgender youth: default mode functional connectivity. Cereb. Cortex 33, 6633–6647 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Franconi, F., Campesi, I., Colombo, D. & Antonini, P. Sex-gender variable: methodological recommendations for increasing scientific value of clinical studies. Cells 8, 476 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kennedy, B. et al. Loss of a parent and the risk of cancer in early life: a nationwide cohort study. Cancer Causes Control 25, 499–506 (2014).

    PubMed  Google Scholar 

  17. Chida, Y., Hamer, M., Wardle, J. & Steptoe, A. Do stress-related psychosocial factors contribute to cancer incidence and survival? Nat. Clin. Pract. Oncol. 5, 466–475 (2008).

    Article  PubMed  Google Scholar 

  18. Yang, T. et al. Work stress and the risk of cancer: a meta-analysis of observational studies. Int. J. Cancer 144, 2390–2400 (2019).

    Article  CAS  PubMed  Google Scholar 

  19. Schoemaker, M. J. et al. Psychological stress, adverse life events and breast cancer incidence: a cohort investigation in 106,000 women in the United Kingdom. Breast Cancer Res. 18, 72 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Butow, P. et al. Does stress increase risk of breast cancer? A 15-year prospective study. Psychooncology 27, 1908–1914 (2018).

    Article  PubMed  Google Scholar 

  21. Choi, Y., Kim, J. K. & Yoo, J. Y. NFκB and STAT3 synergistically activate the expression of FAT10, a gene counteracting the tumor suppressor p53. Mol. Oncol. 8, 642–655 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gonzalez-Aponte, M. F. et al. Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host. Cancer Cell 43, 144–160.e7 (2025).

    Article  CAS  PubMed  Google Scholar 

  23. Schwarzlmueller, P. et al. Steroid hormones as modulators of anti-tumoural immunity. Nat. Rev. Endocrinol. https://doi.org/10.1038/s41574-025-01102-2 (2025).

    Article  PubMed  Google Scholar 

  24. Oyola, M. G. & Handa, R. J. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity. Stress 20, 476–494 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Le Mevel, J. C., Abitbol, S., Beraud, G. & Maniey, J. Temporal changes in plasma adrenocorticotropin concentration after repeated neurotropic stress in male and female rats. Endocrinology 105, 812–817 (1979).

    Article  PubMed  Google Scholar 

  26. Young, E. A. Sex differences in response to exogenous corticosterone: a rat model of hypercortisolemia. Mol. Psychiatry 1, 313–319 (1996).

    CAS  PubMed  Google Scholar 

  27. Verma, R., Balhara, Y. P. & Gupta, C. S. Gender differences in stress response: role of developmental and biological determinants. Ind. Psychiatry J. 20, 4–10 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Handa, R. J., Burgess, L. H., Kerr, J. E. & O’Keefe, J. A. Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis. Horm. Behav. 28, 464–476 (1994).

    Article  CAS  PubMed  Google Scholar 

  29. Khadka, S., Druffner, S. R., Duncan, B. C. & Busada, J. T. Glucocorticoid regulation of cancer development and progression. Front. Endocrinol. 14, 1161768 (2023).

    Article  Google Scholar 

  30. Ruiz, A. M. et al. An integrative literature review and critical reflection of intersectionality theory. Nurs. Inq. 28, e12414 (2021).

    Article  PubMed  Google Scholar 

  31. Lu, J. et al. An egg-adult association, gender, and reproduction in pterosaurs. Science 331, 321–324 (2011).

    Article  PubMed  Google Scholar 

  32. Suvorov, A. Modalities of aging in organisms with different strategies of resource allocation. Ageing Res. Rev. 82, 101770 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Fisher, D. O., Dickman, C. R., Jones, M. E. & Blomberg, S. P. Sperm competition drives the evolution of suicidal reproduction in mammals. Proc. Natl Acad. Sci. USA 110, 17910–17914 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gutierrez-Adan, A. et al. Developmental consequences of sexual dimorphism during pre-implantation embryonic development. Reprod. Domest. Anim. 41, 54–62 (2006).

    Article  PubMed  Google Scholar 

  35. Ray, P. F., Conaghan, J., Winston, R. M. & Handyside, A. H. Increased number of cells and metabolic activity in male human preimplantation embryos following in vitro fertilization. J. Reprod. Fertil. 104, 165–171 (1995).

    Article  CAS  PubMed  Google Scholar 

  36. Tsunoda, Y., Tokunaga, T. & Sugie, T. Altered sex ratio of live young after transfer of fast- and slow-developing mouse embryos. Mol. Rep. Dev. 12, 301–304 (1985).

    Google Scholar 

  37. Darwin, C. Origin of the Species (Macmillan Collector’s Library, 2017).

  38. Rubin, J. B. et al. Epigenetic developmental mechanisms underlying sex differences in cancer. J. Clin. Invest. 134, https://doi.org/10.1172/JCI180071 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tiffin, G. J., Rieger, D., Betteridge, K. J., Yadav, B. R. & King, W. A. Glucose and glutamine metabolism in pre-attachment cattle embryos in relation to sex and stage of development. J. Reprod. Fertil. 93, 125–132 (1991).

    Article  CAS  PubMed  Google Scholar 

  40. Hunter, S. K. & Senefeld, J. W. Sex differences in human performance. J. Physiol. 602, 4129–4156 (2024).

    Article  CAS  PubMed  Google Scholar 

  41. Stanyon, R. & Bigoni, F. Sexual selection and the evolution of behavior, morphology, neuroanatomy and genes in humans and other primates. Neurosci. Biobehav. Rev. 46P4, 579–590 (2014).

    Article  PubMed  Google Scholar 

  42. Lenz, K. M., Nugent, B. M., Haliyur, R. & McCarthy, M. M. Microglia are essential to masculinization of brain and behavior. J. Neurosci. 33, 2761–2772 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Caulin, A. F. & Maley, C. C. Peto’s Paradox: evolution’s prescription for cancer prevention. Trends Ecol. Evol. 26, 175–182 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Smith, G. D., Shipley, M. & Leon, D. A. Height and mortality from cancer among men: prospective observational study. BMJ 317, 1351–1352 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Green, J. et al. Height and cancer incidence in the million women study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol. 12, 785–794 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Tomasetti, C. et al. Role of stem-cell divisions in cancer risk. Nature 548, E13–E14 (2017).

    Article  CAS  PubMed  Google Scholar 

  47. Frankel, S., Gunnell, D. J., Peters, T. J., Maynard, M. & Smith, G. D. Childhood energy intake and adult mortality from cancer: the Boyd Orr cohort study. BMJ 316, 499–504 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Estrella, C. A. S. et al. Asymmetric growth-limiting development of the female conceptus. Front. Endocrinol. 14, 1306513 (2023).

    Article  Google Scholar 

  49. Centers for Disease Control and Prevention, National Center for Health Statistics. WHO Growth Standards Are Recommended for Use in the U.S. for Infants and Children 0 to 2 Years of Age https://www.cdc.gov/growthcharts/who_charts.htm (2010).

  50. Nunney, L. Size matters: height, cell number and a person’s risk of cancer. Proc. Biol. Sci. 285, https://doi.org/10.1098/rspb.2018.1743 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Lemaitre, J. F. et al. The influence of early-life allocation to antlers on male performance during adulthood: evidence from contrasted populations of a large herbivore. J. Anim. Ecol. 87, 921–932 (2018).

    Article  PubMed  Google Scholar 

  52. Lemaitre, J. F. et al. Sex differences in adult lifespan and aging rates of mortality across wild mammals. Proc. Natl Acad. Sci. USA 117, 8546–8553 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tombak, K. J., Hex, S. & Rubenstein, D. I. New estimates indicate that males are not larger than females in most mammal species. Nat. Commun. 15, 1872 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lahdenpera, M., Mar, K. U. & Lummaa, V. Nearby grandmother enhances calf survival and reproduction in Asian elephants. Sci. Rep. 6, 27213 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Martinez de Toda, I. et al. Sex differences in markers of oxidation and inflammation. Implications for ageing. Mech. Ageing Dev. 211, 111797 (2023).

    Article  CAS  PubMed  Google Scholar 

  56. Podolskiy, D. I., Lobanov, A. V., Kryukov, G. V. & Gladyshev, V. N. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development. Nat. Commun. 7, 12157 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tiberi, J. et al. Sex differences in antioxidant defence and the regulation of redox homeostasis in physiology and pathology. Mech. Ageing Dev. 211, 111802 (2023).

    Article  CAS  PubMed  Google Scholar 

  58. Knewtson, K. E., Ohl, N. R. & Robinson, J. L. Estrogen signaling dictates musculoskeletal stem cell behavior: sex differences in tissue repair. Tissue Eng. Part B Rev. 28, 789–812 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Shi, Y. et al. Sex difference in human diseases: mechanistic insights and clinical implications. Signal Transduct. Target. Ther. 9, 238 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Broestl, L. et al. Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma. Commun. Biol. 5, 781 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Yang, W. et al. Sex differences in GBM revealed by analysis of patient imaging, transcriptome, and survival data. Sci. Transl. Med. 11, https://doi.org/10.1126/scitranslmed.aao5253 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Chhabra, Y. et al. Sex-dependent effects in the aged melanoma tumor microenvironment influence invasion and resistance to targeted therapy. Cell 187, 6016–6034.e25 (2024).

    Article  CAS  PubMed  Google Scholar 

  63. Forma, E., Jozwiak, P., Brys, M. & Krzeslak, A. The potential role of O-GlcNAc modification in cancer epigenetics. Cell. Mol. Biol. Lett. 19, 438–460 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ji, J., Zoller, B., Sundquist, J. & Sundquist, K. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: a national cohort study. Int. J. Cancer 139, 754–758 (2016).

    Article  CAS  PubMed  Google Scholar 

  65. Popotas, A., Casimir, G. J., Corazza, F. & Lefevre, N. Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response? Front. Immunol. 15, 1379754 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Haupt, S. et al. Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network. Nat. Commun. 10, 5385 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Chen, X. et al. Sex difference in neural tube defects in p53-null mice is caused by differences in the complement of X not Y genes. Dev. Neurobiol. 68, 265–273 (2008).

    Article  CAS  PubMed  Google Scholar 

  68. Zhang, D. et al. Inactivation of KDM6A promotes the progression of colorectal cancer by enhancing the glycolysis. Eur. J. Med. Res. 29, 310 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tran, N., Broun, A. & Ge, K. Lysine demethylase KDM6A in differentiation, development, and cancer. Mol. Cell. Biol. 40, https://doi.org/10.1128/MCB.00341-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Kaneko, S. & Li, X. X chromosome protects against bladder cancer in females via a KDM6A-dependent epigenetic mechanism. Sci. Adv. 4, eaar5598 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Shen, L. et al. DDX3 acts as a tumor suppressor in colorectal cancer as loss of DDX3 in advanced cancer promotes tumor progression by activating the MAPK pathway. Int. J. Biol. Sci. 18, 3918–3933 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Patmore, D. M. et al. DDX3X suppresses the susceptibility of hindbrain lineages to medulloblastoma. Dev. Cell 54, 455–470.e5 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Dunford, A. et al. Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias. Nat. Genet. 49, 10–16 (2017).

    Article  CAS  PubMed  Google Scholar 

  74. Pierre, R. V. & Hoagland, H. C. Age-associated aneuploidy: loss of Y chromosome from human bone marrow cells with aging. Cancer 30, 889–894 (1972).

    Article  CAS  PubMed  Google Scholar 

  75. Ly, P. et al. Selective Y centromere inactivation triggers chromosome shattering in micronuclei and repair by non-homologous end joining. Nat. Cell Biol. 19, 68–75 (2017).

    Article  CAS  PubMed  Google Scholar 

  76. Mitchell, E. et al. Clonal dynamics of haematopoiesis across the human lifespan. Nature 606, 343–350 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Forsberg, L. A. et al. Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer. Nat. Genet. 46, 624–628 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Abdel-Hafiz, H. A. et al. Y chromosome loss in cancer drives growth by evasion of adaptive immunity. Nature 619, 624–631 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Mattisson, J. et al. Loss of chromosome Y in regulatory T cells. BMC Genomics 25, 243 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Li, J. et al. Histone demethylase KDM5D upregulation drives sex differences in colon cancer. Nature 619, 632–639 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Li, Y., Zhang, D. J., Qiu, Y., Kido, T. & Lau, Y. C. The Y-located proto-oncogene TSPY exacerbates and its X-homologue TSPX inhibits transactivation functions of androgen receptor and its constitutively active variants. Hum. Mol. Genet. 26, 901–912 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Dhanoa, J. K., Mukhopadhyay, C. S. & Arora, J. S. Y-chromosomal genes affecting male fertility: a review. Vet. World 9, 783–791 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Balaresque, P. et al. Y-chromosome descent clusters and male differential reproductive success: young lineage expansions dominate Asian pastoral nomadic populations. Eur. J. Hum. Genet. 23, 1413–1422 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Zerjal, T. et al. The genetic legacy of the mongols. Am. J. Hum. Genet. 72, 717–721 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Frank, S. A. & Hurst, L. D. Mitochondria and male disease. Nature 383, 224 (1996).

    Article  CAS  PubMed  Google Scholar 

  86. Radzvilavicius, A., Layh, S., Hall, M. D., Dowling, D. K. & Johnston, I. G. Sexually antagonistic evolution of mitochondrial and nuclear linkage. J. Evol. Biol. 34, 757–766 (2021).

    Article  CAS  PubMed  Google Scholar 

  87. Mauvais-Jarvis, F. Sex differences in energy metabolism: natural selection, mechanisms and consequences. Nat. Rev. Nephrol. 20, 56–69 (2024).

    Article  PubMed  Google Scholar 

  88. Wallace, D. C. Genetics: mitochondrial DNA in evolution and disease. Nature 535, 498–500 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Gebert, C. et al. DNA methylation in the IGF2 intragenic DMR is re-established in a sex-specific manner in bovine blastocysts after somatic cloning. Genomics 94, 63–69 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Lumey, L. H., Stein, A. D., Kahn, H. S. & Romijn, J. A. Lipid profiles in middle-aged men and women after famine exposure during gestation: the Dutch hunger winter families study. Am. J. Clin. Nutr. 89, 1737–1743 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ravelli, A. C., van Der Meulen, J. H., Osmond, C., Barker, D. J. & Bleker, O. P. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am. J. Clin. Nutr. 70, 811–816 (1999).

    Article  CAS  PubMed  Google Scholar 

  92. Veenendaal, M. V. et al. Transgenerational effects of prenatal exposure to the 1944-45 Dutch famine. BJOG 120, 548–553 (2013).

    Article  CAS  PubMed  Google Scholar 

  93. Vagero, D., Pinger, P. R., Aronsson, V. & van den Berg, G. J. Paternal grandfather’s access to food predicts all-cause and cancer mortality in grandsons. Nat. Commun. 9, 5124 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Bygren, L. O. et al. Change in paternal grandmothers’ early food supply influenced cardiovascular mortality of the female grandchildren. BMC Genet. 15, 12 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  95. van den Berg, G. J. & Pinger, P. R. Transgenerational effects of childhood conditions on third generation health and education outcomes. Econ. Hum. Biol. 23, 103–120 (2016).

    Article  PubMed  Google Scholar 

  96. Maher, E. R. & Reik, W. Beckwith-Wiedemann syndrome: imprinting in clusters revisited. J. Clin. Invest. 105, 247–252 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Harvey, M. B. & Kaye, P. L. IGF-2 stimulates growth and metabolism of early mouse embryos. Mech. Dev. 38, 169–173 (1992).

    Article  CAS  PubMed  Google Scholar 

  98. Azzi, S. et al. Multilocus methylation analysis in a large cohort of 11p15-related foetal growth disorders (Russell Silver and Beckwith Wiedemann syndromes) reveals simultaneous loss of methylation at paternal and maternal imprinted loci. Hum. Mol. Genet. 18, 4724–4733 (2009).

    Article  CAS  PubMed  Google Scholar 

  99. Latos, P. A. et al. Airn transcriptional overlap, but not its lncRNA products, induces imprinted Igf2r silencing. Science 338, 1469–1472 (2012).

    Article  CAS  PubMed  Google Scholar 

  100. Ferguson-Smith, A. C. & Surani, M. A. Imprinting and the epigenetic asymmetry between parental genomes. Science 293, 1086–1089 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Peters, J. The role of genomic imprinting in biology and disease: an expanding view. Nat. Rev. Genet. 15, 517–530 (2014).

    Article  CAS  PubMed  Google Scholar 

  102. Faisal, M., Kim, H. & Kim, J. Sexual differences of imprinted genes’ expression levels. Gene 533, 434–438 (2014).

    Article  CAS  PubMed  Google Scholar 

  103. Tan, Q. et al. Age patterns of intra-pair DNA methylation discordance in twins: sex difference in epigenomic instability and implication on survival. Aging Cell 20, e13460 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Grant, O. A., Wang, Y., Kumari, M., Zabet, N. R. & Schalkwyk, L. Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array. Clin. Epigenetics 14, 62 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Terao, M. et al. Turnover of mammal sex chromosomes in the Sry-deficient Amami spiny rat is due to male-specific upregulation of Sox9. Proc. Natl Acad. Sci. USA 119, e2211574119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Koopman, P., Gubbay, J., Vivian, N., Goodfellow, P. & Lovell-Badge, R. Male development of chromosomally female mice transgenic for Sry. Nature 351, 117–121 (1991).

    Article  CAS  PubMed  Google Scholar 

  107. De Vries, G. J. et al. A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits. J. Neurosci. 22, 9005–9014 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Arnold, A. P. & Chen, X. What does the “four core genotypes” mouse model tell us about sex differences in the brain and other tissues? Front. Neuroendocrinol. 30, 1–9 (2009).

    Article  PubMed  Google Scholar 

  109. Guo, X., Puttabyatappa, M., Domino, S. E. & Padmanabhan, V. Developmental programming: prenatal testosterone-induced changes in epigenetic modulators and gene expression in metabolic tissues of female sheep. Mol. Cell. Endocrinol. 514, 110913 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Matsuda, K. I. et al. Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior. Endocrinology 152, 2760–2767 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Nugent, B. M. et al. Brain feminization requires active repression of masculinization via DNA methylation. Nat. Neurosci. 18, 690–697 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Johansen, M. L. et al. Gliomas display distinct sex-based differential methylation patterns based on molecular subtype. Neurooncol. Adv. 2, vdaa002 (2020).

    PubMed  PubMed Central  Google Scholar 

  113. Ren, Y. et al. Gender specificity improves the early-stage detection of clear cell renal cell carcinoma based on methylomic biomarkers. Biomark. Med. 12, 607–618 (2018).

    Article  CAS  PubMed  Google Scholar 

  114. Lin, S. et al. Sex-related DNA methylation differences in B cell chronic lymphocytic leukemia. Biol. Sex Differ. 10, 2 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  115. Kundakovic, M. & Tickerhoof, M. Epigenetic mechanisms underlying sex differences in the brain and behavior. Trends Neurosci. 47, 18–35 (2024).

    Article  CAS  PubMed  Google Scholar 

  116. Yoh, K., Ikeda, K., Horie, K. & Inoue, S. Roles of estrogen, estrogen receptors, and estrogen-related receptors in skeletal muscle: regulation of mitochondrial function. Int. J. Mol. Sci. 24, https://doi.org/10.3390/ijms24031853 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Spoletini, I., Vitale, C., Malorni, W. & Rosano, G. M. Sex differences in drug effects: interaction with sex hormones in adult life. Handb. Exp. Pharmacol. 214, 91–105 (2012).

    Article  CAS  Google Scholar 

  118. Ucciferri, C. C. & Dunn, S. E. Effect of puberty on the immune system: relevance to multiple sclerosis. Front. Pediatr. 10, 1059083 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Deamer, W. C. Stimulation of growth in boys by sublingual testosterone therapy. Am. J. Dis. Child. 75, 850–859 (1948).

    CAS  Google Scholar 

  120. Fujita, K. Cytochrome P450 and anticancer drugs. Curr. Drug. Metab. 7, 23–37 (2006).

    Article  CAS  PubMed  Google Scholar 

  121. Naqvi, S. et al. Conservation, acquisition, and functional impact of sex-biased gene expression in mammals. Science 365, https://doi.org/10.1126/science.aaw7317 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Berner, A. M. & Atkinson, S. E. The implications of hormone treatment for cancer risk, screening and treatment in transgender individuals. Best Pract. Res. Clin. Endocrinol. Metab. 38, 101909 (2024).

    Article  CAS  PubMed  Google Scholar 

  123. Pott, P. Chirurgical Observations Relative to the Cataract, the Polypus of the Nose, and Cancer of the Scrotum (1775).

  124. Dijksterhuis, W. P. M. et al. Gender differences in treatment allocation and survival of advanced gastroesophageal cancer: a population-based study. J. Natl Cancer Inst. 113, 1551–1560 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Sarasqueta, C. et al. Gender differences in stage at diagnosis and preoperative radiotherapy in patients with rectal cancer. BMC Cancer 20, 759 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Din, N. U. et al. Age and gender variations in cancer diagnostic intervals in 15 cancers: analysis of data from the UK clinical practice research datalink. PLoS One 10, e0127717 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Kalathoor, S. et al. Representation of women in clinical trials supporting FDA-approval of contemporary cancer therapies. Int. J. Cancer 155, 1958–1968 (2024).

    Article  CAS  PubMed  Google Scholar 

  128. Pala, L., De Pas, T. & Conforti, F. Under-representation of women in randomized clinical trials testing anticancer immunotherapy may undermine female patients care. a call to action. Semin. Oncol. 49, 400–404 (2022).

    Article  CAS  PubMed  Google Scholar 

  129. Bierer, B. E., Meloney, L. G., Ahmed, H. R. & White, S. A. Advancing the inclusion of underrepresented women in clinical research. Cell Rep. Med. 3, 100553 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Widdowson, E. M. The response of the sexes to nutritional stress. Proc. Nutr. Soc. 35, 175–180 (1976).

    Article  CAS  PubMed  Google Scholar 

  131. Grayson, D. Differential mortality and the donner party disaster. Evol. Anthropol. 2, 151–150 (1993).

    Article  Google Scholar 

  132. Zarulli, V. et al. Women live longer than men even during severe famines and epidemics. Proc. Natl Acad. Sci. USA 115, E832–E840 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Krumsiek, J. et al. Gender-specific pathway differences in the human serum metabolome. Metabolomics 11, 1815–1833 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Sponagel, J. et al. Sex differences in brain tumor glutamine metabolism reveal sex-specific vulnerabilities to treatment. Med 3, 792–811.e12 (2022).

    Article  CAS  PubMed  Google Scholar 

  135. Ippolito, J. E., Yim, A. K., Luo, J., Chinnaiyan, P. & Rubin, J. B. Sexual dimorphism in glioma glycolysis underlies sex differences in survival. JCI Insight 2, https://doi.org/10.1172/jci.insight.92142 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Menezo, Y. J., Chouteau, J., Torello, J., Girard, A. & Veiga, A. Birth weight and sex ratio after transfer at the blastocyst stage in humans. Fertil. Steril. 72, 221–224 (1999).

    Article  CAS  PubMed  Google Scholar 

  137. Prochazkova, M. et al. Vegan diet is associated with favorable effects on the metabolic performance of intestinal microbiota: a cross-sectional multi-omics study. Front. Nutr. 8, 783302 (2021).

    Article  PubMed  Google Scholar 

  138. Connolly-Schoonen, J. et al. A pilot controlled feeding trial modifying protein intake in healthy subjects to assess adherence and the metabolome. Nutr. Cancer 75, 1499–1510 (2023).

    Article  CAS  PubMed  Google Scholar 

  139. Santangelo, C. et al. Dietary habits, physical activity and body mass index in transgender and gender diverse adults in Italy: a voluntary sampling observational study. Nutrients 16, https://doi.org/10.3390/nu16183139 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Lyu, W., Yu, L. & Lv, H. Gender wage gap and child malnutrition in Ethiopia: a probit instrumental variable method. Heliyon 10, e37000 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Ahmed, F. et al. Political economy of maternal child malnutrition: experiences about water, food, and nutrition policies in Pakistan. Nutrients 16, https://doi.org/10.3390/nu16162642 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Yang, W. & Rubin, J. B. Treating sex and gender differences as a continuous variable can improve precision cancer treatments. Biol. Sex Differ. 15, 35 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Conforti, F. et al. Sex-based heterogeneity in response to lung cancer immunotherapy: a systematic review and meta-analysis. J. Natl Cancer Inst. 111, 772–781 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Conforti, F. et al. Sex-based dimorphism of anticancer immune response and molecular mechanisms of immune evasion. Clin. Cancer Res. 27, 4311–4324 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Conforti, F. et al. Sex-based differences in response to anti-PD-1 or PD-L1 treatment in patients with non-small-cell lung cancer expressing high PD-L1 levels. A systematic review and meta-analysis of randomized clinical trials. ESMO Open 6, 100251 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Santoni, M. et al. The impact of gender on the efficacy of immune checkpoint inhibitors in cancer patients: the MOUSEION-01 study. Crit. Rev. Oncol. Hematol. 170, 103596 (2022).

    Article  PubMed  Google Scholar 

  147. Chakrabarty, A., Chakraborty, S., Nandi, D. & Basu, A. Multivariate genetic architecture reveals testosterone-driven sexual antagonism in contemporary humans. Proc. Natl Acad. Sci. USA 121, e2404364121 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Bland, H. T. et al. Conducting inclusive research in genetics for transgender, gender-diverse, and sex-diverse individuals: case analyses and recommendations from a clinical genomics study. J. Genet. Couns. 33, 772–785 (2024).

    Article  PubMed  Google Scholar 

  149. Hanson, K. et al. Understanding the intersection of identity and cancer experience among racially, ethnically, gender and sexual minoritized adolescents and young adults with cancer. Psychooncology 33, e70000 (2024).

    Article  PubMed  Google Scholar 

  150. Martinez, A., Delpierre, C., Grosclaude, P. & Lamy, S. Integrating gender into cancer research. Lancet 403, 1631 (2024).

    Article  PubMed  Google Scholar 

  151. Gehrels, A. M. et al. Gender differences in tumor characteristics, treatment allocation and survival in stage I-III pancreatic cancer: a nationwide study. Eur. J. Cancer 206, 114117 (2024).

    Article  CAS  PubMed  Google Scholar 

  152. Stenzel, A. E. et al. Discrimination in the medical setting among LGBTQ+ adults and associations with cancer screening. Cancer Causes Control https://doi.org/10.1007/s10552-024-01927-8 (2024).

    Article  PubMed  Google Scholar 

  153. Kfoury, N. et al. Brd4-bound enhancers drive cell-intrinsic sex differences in glioblastoma. Proc. Natl Acad. Sci. USA 118, https://doi.org/10.1073/pnas.2017148118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  154. Kfoury, N. et al. Cooperative p16 and p21 action protects female astrocytes from transformation. Acta Neuropathol. Commun. 6, 12 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Klein, S. L. & Flanagan, K. L. Sex differences in immune responses. Nat. Rev. Immunol. 16, 626–638 (2016).

    Article  CAS  PubMed  Google Scholar 

  156. Figtree, G. A., Noonan, J. E., Bhindi, R. & Collins, P. Estrogen receptor polymorphisms: significance to human physiology, disease and therapy. Recent. Pat. DNA Gene Seq. 3, 164–171 (2009).

    Article  CAS  PubMed  Google Scholar 

  157. Giovannucci, E. et al. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc. Natl Acad. Sci. USA 94, 3320–3323 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Han, G. et al. The AIB1 gene polyglutamine repeat length polymorphism contributes to risk of epithelial ovarian cancer risk: a case-control study. Tumour Biol. 36, 371–374 (2015).

    Article  PubMed  Google Scholar 

  159. Wang, Q., Udayakumar, T. S., Vasaitis, T. S., Brodie, A. M. & Fondell, J. D. Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells. J. Biol. Chem. 279, 17319–17328 (2004).

    Article  CAS  PubMed  Google Scholar 

  160. He, Y. et al. Androgen receptor with short polyglutamine tract preferably enhances Wnt/β-catenin-mediated prostatic tumorigenesis. Oncogene 39, 3276–3291 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Perret, M. Litter sex composition affects first reproduction in female grey mouse lemurs (Microcebus murinus). Physiol. Behav. 208, 112575 (2019).

    Article  CAS  PubMed  Google Scholar 

  162. Monclus, R. & Blumstein, D. T. Litter sex composition affects life-history traits in yellow-bellied marmots. J. Anim. Ecol. 81, 80–86 (2012).

    Article  PubMed  Google Scholar 

  163. Yang, W., Wong, J. & Rubin, J. Sex and Gender: Transforming Scientific Practice Vol. 36 (Springer-Nature, 2025).

  164. Mauvais-Jarvis, F. et al. Sex- and gender-based pharmacological response to drugs. Pharmacol. Rev. 73, 730–762 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Patwardhan, V. et al. Differences across the lifespan between females and males in the top 20 causes of disease burden globally: a systematic analysis of the global burden of disease study 2021. Lancet Public Health 9, e282–e294 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Vera, R., Juan-Vidal, O., Safont-Aguilera, M. J., de la Pena, F. A. & Del Alba, A. G. Sex differences in the diagnosis, treatment and prognosis of cancer: the rationale for an individualised approach. Clin. Transl. Oncol. 25, 2069–2076 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Whitmire, P. et al. Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients. BMC Cancer 20, 447 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Rakshith, H. T., Lohita, S., Rebello, A. P., Goudanavar, P. S. & Raghavendra Naveen, N. Sex differences in drug effects and/or toxicity in oncology. Curr. Res. Pharmacol. Drug Discov. 4, 100152 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Dong, M. et al. Sex differences in cancer incidence and survival: a pan-cancer analysis. Cancer Epidemiol. Biomark. Prev. 29, 1389–1397 (2020).

    Article  Google Scholar 

  170. Goh, R. et al. Resuscitation orders demonstrate differences by gender, stroke type and intervention. J. Stroke Cerebrovasc. Dis. 33, 107881 (2024).

    Article  PubMed  Google Scholar 

  171. Cathcart-Rake, E. J. et al. Sexual orientation and gender identity data collection in cancer care: a nationwide landscape assessment update. JCO Oncol. Pract. 20, 1272–1279 (2024).

    Article  PubMed  Google Scholar 

  172. Triplette, M. et al. A multistakeholder qualitative study to inform sexual orientation and gender identity data collection in the cancer care setting. LGBT Health https://doi.org/10.1089/lgbt.2024.0065 (2024).

    Article  PubMed  Google Scholar 

  173. Wheldon, C. W., Sklarz, T. & Frosch, Z. A. K. Advancing equity in cancer care: the critical role of sexual orientation and gender identity data collection. JCO Oncol. Pract. 20, 1146–1148 (2024).

    Article  PubMed  Google Scholar 

  174. Hunt, L., Nielsen, M. W. & Schiebinger, L. A framework for sex, gender, and diversity analysis in research. Science 377, 1492–1495 (2022).

    Article  CAS  PubMed  Google Scholar 

  175. Rajendran, A. et al. Sex-specific differences in cardiovascular risk factors and implications for cardiovascular disease prevention in women. Atherosclerosis 384, 117269 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Stamellou, E. et al. Sex-specific differences in kidney function and blood pressure regulation. Int. J. Mol. Sci. 25, https://doi.org/10.3390/ijms25168637 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  177. Cherubini, A., Della Torre, S., Pelusi, S. & Valenti, L. Sexual dimorphism of metabolic dysfunction-associated steatotic liver disease. Trends Mol Med. https://doi.org/10.1016/j.molmed.2024.05.013 (2024).

    Article  PubMed  Google Scholar 

  178. Gardner, D. K. & Leese, H. J. Assessment of embryo viability prior to transfer by the noninvasive measurement of glucose uptake. J. Exp. Zool. 242, 103–105 (1987).

    Article  CAS  PubMed  Google Scholar 

  179. Gardner, D. K., Wale, P. L., Collins, R. & Lane, M. Glucose consumption of single post-compaction human embryos is predictive of embryo sex and live birth outcome. Hum. Reprod. 26, 1981–1986 (2011).

    Article  CAS  PubMed  Google Scholar 

  180. Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).

    PubMed  Google Scholar 

  181. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. DietaryGuidelines.gov (2020).

  182. Batheja, D., Goel, S. & Charani, E. Understanding gender inequities in antimicrobial resistance: role of biology, behaviour and gender norms. BMJ Glob. Health 10, https://doi.org/10.1136/bmjgh-2024-016711 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Gibbs, D. L. et al. Robust cluster prediction across data types validates association of sex and therapy response in GBM. Cancers 17, https://doi.org/10.3390/cancers17030445 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  184. Mauvais-Jarvis, F. et al. Sex and gender: modifiers of health, disease, and medicine. Lancet 396, 565–582 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  185. Funer, F. Admitting the heterogeneity of social inequalities: intersectionality as a (self-)critical framework and tool within mental health care. Philos. Ethics Humanit. Med. 18, 21 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  186. Enaifoghe, A. The influence of culture and gender differences in communication: society’s perception. Res. Bus. Soc. Sci. 12, 460–468 (2023).

    Google Scholar 

Download references

Acknowledgements

I would like to acknowledge all the people who have discussed these topics with me over the years. Work on sex differences in the Rubin lab is supported by R01 CA174737-07, NIH PO1 CA245705, Joshua’s Great Things and The St Louis Children’s Hospital Foundation.

Author information

Authors and Affiliations

  1. Department of Paediatrics, Washington University School of Medicine, St Louis, MO, USA

    Joshua B. Rubin

  2. Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA

    Joshua B. Rubin

Authors
  1. Joshua B. Rubin
    View author publications

    Search author on:PubMed Google Scholar

Contributions

The author handled all aspects of the article.

Corresponding author

Correspondence to Joshua B. Rubin.

Ethics declarations

Competing interests

The author declares no competing interests.

Peer review

Peer review information

Nature Reviews Cancer thanks Xue Li, who co-reviewed with Singha Biplab and Gian-Paolo Dotto, who co-reviewed with Jovan Isma, for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

Dietary guidelines of the U.S. Department of Agriculture and U.S. Department of Health and Human Services: DietaryGuidelines.gov: https://www.fns.usda.gov/cnpp/dietary-guidelines-americans

Electronic Human Relations Area Files (eHRAF): https://ehrafworldcultures.yale.edu/

Glossary

Anabolism

The process of building complex molecules from simple ones.

Anthropomorphic

Attribution of human traits to animals.

Bayesian statistical approach

Bayesian statistics are distinct as they incorporate prior knowledge into prior probability distributions allowing for each new piece of data to be incorporated into prior knowledge such that prior probability distributions for each iteration of an experiment can change.

Consomic Y model

Consomic strains of inbred mice possess single chromosomes, like a Y chromosome, derived from another strain through a series of backcrosses.

Darwinopterus

Darwinopterus is a pterosaur, named after Charles Darwin, that lived between 150 and 170 million years ago.

Default mode network

A large-scale functional brain network that is most active when an individual is not interacting with the outside world, such as when they are resting, daydreaming, thinking about themselves and others, remembering or planning.

DNA imprints

An epigenetic phenomenon involving DNA methylation in gametes that results in genes being expressed or not as a function of whether they were maternally or paternally inherited.

Gender

Human traits and behaviours that derive from self-identity interacting with social and cultural expectations about what it means to be a man, a woman or non-binary.

Gender–sex interaction

(GSI). The complex ways in which gender and sex interact to determine an individual’s phenotype and life experience.

Hominidae

The taxonomic primate family, also known as the great apes, that includes orangutans, gorillas, chimpanzees and humans.

Hypothalamic–pituitary–adrenal axis

A brain–body system for the regulation of endocrinological responses to stress.

Intersectionality

A sociological paradigm for integrating the multiple unique contributions of systematized privilege and discrimination to an individual’s life.

Marsupial

Marsupials are mammals that are distinguished by having both placentae for early gestational development and an external pouch in which the completion of gestation takes place.

Meiotic crossing-over

Chromosomal crossover occurs during meiosis between two homologous chromosomes to produce new recombinant chromosomes.

Mode

A statistical term meaning the most common value in a dataset.

Polymorphic variation

The condition of there being more than one allele of the same gene that differs in DNA sequence within a population.

Sex

The shared reproductive biology between humans and other sexually reproducing mammals.

Transcriptomic index approach

A Bayesian-based analysis of cancer transcriptomes that supports deeper phenotyping of patients for treatment stratification based on their similarity to other patients of the same sex.

Wilms tumour

A rare kidney cancer that most commonly affects young children.

Y allele

Variation in the sequences of Y-encoded genes within a population.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rubin, J.B. Gender and sex interactions are intrinsic components of cancer phenotypes. Nat Rev Cancer 25, 634–648 (2025). https://doi.org/10.1038/s41568-025-00829-4

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41568-025-00829-4

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer