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Sexual dimorphism in cancer

Abstract

The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment.

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Figure 1: Major cancer types, in organs unrelated to reproductive function, with gender differences in incidence and mortality.
Figure 2: Role of sex steroid hormone receptors in non-reproductive tissues.
Figure 3: Possible mechanisms contributing to gender dimorphism in hepatocellular carcinoma.
Figure 4: Interplay between sex chromosomes in human cancer.
Figure 5: Hormonal and chromosomal contributions to sexual dimorphism in cancer.

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Acknowledgements

This work was supported by grants from Swiss National Science Foundation (310030_156191/1), US National Institutes of Health (NIH; R01AR039190; R01AR064786; the content not necessarily representing the official views of NIH), European Research Council (26075083) and OncoSuisse (OCS-2922-02-2012). A.C. is supported by an AIRC-EU FP7 Marie Curie Fellowship granted by the Italian Association for Cancer Research and the European Union FP7 Marie Curie Program.

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Clocchiatti, A., Cora, E., Zhang, Y. et al. Sexual dimorphism in cancer. Nat Rev Cancer 16, 330–339 (2016). https://doi.org/10.1038/nrc.2016.30

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