SeXX-based cancer

Elena Zanchini di Castiglionchio on the genetic and hormonal basis of sex differences in cancer


The recent discovery of the biological basis for sex-based differences in health has acted as a catalyst for an explosion of understanding in the field of sex medicine.

The incidence of many different types of cancer varies between men and women. Meningioma, a form of usually benign brain tumour, is twice as likely to occur in adult females (30 to 70 years old) than adult males. A study in Japan also found that women are 2.14 times more likely to develop non-urothelial carcinoma than males, a rare form of aggressive bladder cancer. Yet it’s not all doom and gloom for females: gliomas, a normally malignant cancer of the brain’s glial cells, is much more common in males.

This sex-based difference in health has been attributed to the gonadal hormones, produced by the sex organs in males and females. These seem to be linked to differences in tumour rates. The incidence of bladder cancer was shown to be higher in post-menopausal women than in pre-menopausal, probably due to a decrease in the concentration of hormones such as oestrogen after menopause. Many cancers even have receptors that recognise female hormones on their surface, making them responsive to progesterone and oestrogen levels. What’s more, women undertaking hormone replacement therapy have increased risk of developing a meningioma. The same can be said of male prostate cancer patients who’ve had their hormones therapeutically decreased.

However, sex hormones alone are not sufficient to explain all variation between males and females. Scientists have observed differences in brain structure between mice of both sex which have been genetically engineered to prevent the development of sex organs and so are unable to produce sex hormones. This divergence has been attributed to basic genetic differences between the male and female cells.

While male cells contain XY chromosomes, female cells contain XX. Due to its physical size, the X chromosome carries more genes than the Y chromosome. Indeed, female cells must inactivate one of their X chromosomes to prevent over-expression of these genes. When the X chromosome is incompletely inactivated genes found on it are over-expressed, with potentially severe consequences. This is associated with many diseases prevalent in women, including autoimmune diseases such as lupus. Interestingly, men with Klinefelter’s syndrome whose cells contain XXY chromosomes due to a failure of cellular machinery during meiosis (cell division to form sperm or eggs) are more at risk of developing diseases normally prevalent in women. This is most likely due to their increased levels of X chromosome expression.

Scientists are channeling their knowledge of sex-based diseases to combat them. For example, the protective effect of male hormones in inhibiting meningiomas could potentially be used to treat the tumour itself. The field’s innovative perspective on health is primed to revolutionise the way we prescribe medication and treat disease in the near future.