Summary
Major differences in survival of men and women from infectious diseases and cancers have been highlighted by death rates from COVID-19 infections. In cancer, attention has been focussed on differences in gene expression from X chromosomes in men and women with a preponderance of genes involved in immune responses being expressed in women. Important findings have been that some of the genes are important epigenetic regulators that play fundamental roles in immune responses.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Wenham, C., Smith, J. & Morgan, R. COVID-19: the gendered impacts of the outbreak. Lancet 395, 846–848 (2020).
Jin, J.-M., Bai, P., He, W., Wu, F., Liu, X.-F., Han, D.-M. et al. Gender differences in patients with COVID-19: focus on severity and mortality. Front. Public Health 8, 152 (2020).
NYC Health. COVID-19: data. https://www1.nyc.gov/site/doh/covid/covid-19-data.page (2020).
Joosse, A., Collette, S., Suciu, S., Nijsten, T., Patel, P. M., Keilholz, U. et al. Sex is an independent prognostic indicator for survival and relapse/progression-free survival in metastasized stage III to IV melanoma: a pooled analysis of five European organisation for research and treatment of cancer randomized controlled trials. J. Clin. Oncol. 31, 2337–2346 (2013).
Dunford, A., Weinstock, D. M., Savova, V., Schumacher, S. E., Cleary, J. P., Yoda, A. et al. Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias. Nat. Genet. 49, 10–16 (2017).
Australian Institute of Health and Welfare 2019. Cancer in Australia 2019. Cancer series no.119. Cat. no. CAN 123 (AIHW, Canberra, 2019).
Chen, J., Shih, J., Tran, A., Mullane, A., Thomas, C., Aydin, N. et al. Gender-based differences and barriers in skin protection behaviors in melanoma survivors. J. Skin Cancer 2016, 3874572 (2016).
Gupta, S., Artomov, M., Goggins, W., Daly, M. & Tsao, H. Gender disparity and mutation burden in metastatic melanoma. J. Natl Cancer Inst. 107, djv221 (2015).
Libert, C., Dejager, L. & Pinheiro, I. The X chromosome in immune functions: when a chromosome makes the difference. Nat. Rev. Immunol. 10, 594–604 (2010).
Colognori, D., Sunwoo, H., Kriz, A. J., Wang, C.-Y. & Lee, J. T. Xist deletional analysis reveals an interdependency between Xist RNA and polycomb complexes for spreading along the inactive X. Mol. Cell 74, 101.e10–117.e10 (2019).
Wang, J., Syrett, C. M., Kramer, M. C., Basu, A., Atchison, M. L. & Anguera, M. C. Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. Proc. Natl Acad. Sci. USA 113, E2029–E2038 (2016).
Emran, A. A., Nsengimana, J., Punnia-Moorthy, G., Schmitz, U., Gallagher, S. J., Newton-Bishop, J. et al. Study of the female sex survival advantage in melanoma-a focus on X-linked epigenetic regulators and immune responses in two cohorts. Cancers 12, 2082 (2020).
Itoh, Y., Golden, L. C., Itoh, N., Matsukawa, M. A., Ren, E., Tse, V. et al. The X-linked histone demethylase Kdm6a in CD4+ T lymphocytes modulates autoimmunity. J. Clin. Investig. 129, 3852–3863 (2019).
Tiffen, J., Gallagher, S. J., Fabian, F., Dilini, G., Emran, A. A., Cullinane, C. et al. EZH2 cooperates with DNA methylation to downregulate key tumour suppressors and interferon gene signatures in melanoma. J. Investig. Dermatol. 140, 2442.e5–2454.e5 (2020).
Overmyer, K. A., Shishkova, E., Miller, I. J., Balnis, J., Bernstein, M. N., Peters-Clarke, T. M. et al. Large-scale multi-omic analysis of COVID-19 severity. Cell Systems https://doi.org/10.1016/j.cels.2020.10.003 (2020).
Xie, G., Liu, X., Zhang, Y., Li, W., Liu, S., Chen, Z. et al. UTX promotes hormonally responsive breast carcinogenesis through feed-forward transcription regulation with estrogen receptor. Oncogene 36, 5497–5511 (2017).
Breithaupt-Faloppa, A. C., Correia, C. J., Prado, C. M., Stilhano, R. S., Ureshino, R. P. & Moreira, L. F. P. 17β-Estradiol, a potential ally to alleviate SARS-CoV-2 infection. Clinics 75, e1980 (2020).
Acknowledgements
We are grateful to the researchers involved in making their data publicly available in TCGA and in the analysis of COVID-19 severity.
Author information
Authors and Affiliations
Contributions
Conceptualisation—A.A.E., J.C.T. and P.H.; data curation—A.A.E. and S.J.G.; writing, review and editing—P.H., A.A.E. and J.C.T.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Written informed consent of all participants in the TCGA was obtained by the TCGA research network. Ethical approval for the studies on COVID-19 patients was obtained from the Albany Medical College Committee on research as referred to in by Overmyer et al.15 All the studies were performed in accordance with the Declaration of Helsinki.
Data availability
All sources of the publicly available data used in the study are quoted in the commentary.
Competing interests
The authors declare no competing interests.
Funding information
This work was funded by the Australian National Health and Medical Research Council (NHMRC) programme grant-633004 and Cancer Council NSW grant-RG-19-05.
Additional information
Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Emran, A.A., Gallagher, S.J., Tiffen, J.C. et al. Sex bias of females in survival from cancer and infections. Is X the answer?. Br J Cancer 124, 1184–1186 (2021). https://doi.org/10.1038/s41416-020-01245-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41416-020-01245-1