Male and female
Cancer mutations depend on gender
Kirill Stasevich, "Science and Life"
It is known that different types of cancer in men and women occur with different frequency. For example, liver cancer in men can be found three times more often, and in some countries this bias is only increasing. Malignant lung tumors are also more common among men. On the one hand, this may be due to the fact that men and women lead different lifestyles – roughly speaking, men smoke and drink more than women. But on the other hand, the male body is still different from the female, and perhaps the different frequency of the same tumors is associated with some of their own biological characteristics of women and men.
Since cells become malignant due to mutations, it would be natural to assume that there are "female" mutations and "male" mutations. Indeed, there are studies that suggest that with some oncological diseases (for example, with brain tumors and melanoma), the pattern of mutations differs in different sexes. A recent work posted on the bioRxiv portal (Li et al., Sex Differences in Oncogenic Mutational Processes) demonstrates the most complete picture in this sense. The authors of the article analyzed mutations not only in genes (that is, in those parts of DNA that encode proteins), but also in regulatory sequences that control the activity of genes, and for comparison they took many different types of tumors: about 2 thousand samples of 28 types of cancer.
As a result, it turned out that there are point cancer mutations that are more common in men than in women, and vice versa. If we consider cases when large segments of sequences disappear or are duplicated in DNA (which again is fraught with malignant degeneration), then there are 4285 genes in which such large rearrangements also depend on gender.
But the most important thing that was discovered is that mutations in men and women often occur in different ways. Here we need to remind you that we still have mutations, because they were not corrected by the DNA repair (or repair) system. There are several such systems in our cells, they differ in the molecular mechanism and in the damage that they correct. For example, if you need to correct the incorrect pairing of nucleotides in a double DNA chain, one system works, and if the DNA, for example, just broke, and broke with two chains at once, then other enzymes are already working here. By the nature of the mutations, it is possible to understand which kind of repair system worked badly.
And it turned out that if we take all "female" tumors, then in 97% of cases mutations in them will be due to improper pairing of nucleotides; in "male" cancers, mutations of improper pairing will be characteristic of 89% of oncological cases. The difference is most visible on liver tumors: in 88% of cases, these tumors occur in women due to poor work in the repair of incorrectly paired nucleotides, in 58% of men. At the same time, in men, all types of cancer are more likely to develop due to mutations that have arisen due to double breaks in DNA.
It is well known that oncological diseases differ from each other, and even the same tumor at first glance in one patient is treatable, while the other is not. Therefore, it is so important to know what the individual portrait of cancer depends on. Why oncomutations occur in men and women preferably by one or another mechanism and what intersex differences play a role here remains to be seen, but for some practical conclusions, the results obtained can obviously be used right now.
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