Protective Genes

When it comes to cancer, women have the edge over men. Over 20% more men develop and die of cancer in Switzerland, according to figures from the Swiss Cancer League. These differences are evident in the three most common non-sex-specific types of cancer (lung and colorectal cancer and malignant melanoma) and are marked for certain types: men are three times more likely to develop bladder and esophageal cancer than women, while women have a higher risk for thyroid cancer. The two most common cancers – breast and prostate – depend on sex for obvious reasons, although a small number of men do develop breast cancer. However, ovarian cancer only affects women.

These sex-specific differences can be observed all over the world, and they are more pronounced in many countries than in Switzerland. They are all the more striking in that women live significantly longer than men, and the chance of developing cancer increases with age. These differences between men and women were long put down to behavior, as men are more likely to drink alcohol, have a poor diet and smoke – but that is changing. The differences were also explained by occupational hazards, such as chemical factories or pesticides in agriculture – workplaces that used to be male-dominated. In the meantime, however, there is growing evidence that biological differences between men and women are at least partly responsible for the observed difference. In a paper for UZH, physician Alessandra Curioni compiled sex-specific differences in oncology.

If we assume that genetic processes have a role to play in the formation and spread of cancer cells, the genome – the entire set of DNA instructions found in a cell – again becomes a focus of interest. Men are much worse off than women in this regard: instead of two X-chromosomes, they only have one, supplemented by a smaller Y-chromosome that only contains a small number of genes, mainly with specifically male functions. Initial indications suggest that this obvious difference also plays a role in the sex-based tumor differences. The molecular biological processes are fairly complicated, as one of a woman’s two X-chromosomes is inactivated during embryonic development – an evolutionary protective mechanism to equalize the genetic playing field between men and women.

But this inactivation isn’t always complete, causing special genes from the dormant X-chromosome that protects against tumors to be reactivated (tumor suppressor gene). In the case of leukemia, for example, researchers have discovered tumor suppressors that escape X-inactivation. Molecular geneticists working on cancer conclude that the genetic factors on the X-chromosome are likely one of the reasons behind the sex-specific differences. Although tumor suppressor genes also occur on other chromosomes.

And it is not only these protective genes, but also various gene variants in men and women that interfere in biochemical control loops and can encourage sex-specific tumors. On the whole, this molecular genetic research on gender aspects of cancer is still in its infancy. Oncologists therefore also cite well-known biological differences, for example that women generally have stronger immune systems than men. This probably helps their bodies detect and eliminate malignant tumor cells in the early stages.

There are also sex-specific differences in some enzymes that break down and eliminate drugs from the body, which cause active substances to remain active for varying lengths of time. In the case of colorectal cancer, there are some surprising anatomical peculiarities: women are more likely to develop cancer in the upper proximal area, where it is more difficult to diagnose, than in the descending distal area. In colorectal cancer in particular, a whole series of hormonal and genetic factors are now known that can differ by sex. Some experts therefore see this cancer as an example of why greater account should be taken of gender medicine in diagnosis and therapy going forward. But for now, that is still a long way off. “We know that there are sex-specific differences in cancer,” says Anja Lorch, vice director of the Medical Oncology and Hematology Department at University Hospital Zurich. “But not enough research has been done into the causes to derive sex-specific therapies and preventive measures.”  Only when the findings from preclinical and clinical trials are further corroborated will it be possible to develop new approaches such as sex-dependent doses and gender-specific medicines.

This article is part of the dossier on gender medicine from UZH Magazine 1/24.