Gender influences tumor therapy

Differences between men and women may be highly probably therapeutically significant. Particularly in the field of tumor medicine, risks and opportunities depend on the respective sex.

More men respond to checkpoint inhibitors, for example

Differences between men and women may be highly probably therapeutically significant. Particularly in the field of tumor medicine, risks and opportunities depend on the respective sex.

According to one study, gender-specific differences exist in both solid and hematological tumors, which extend down to the DNA level and the changes that occur there. This leads to the fact that for individual tumor entities, e.g. in bile or liver carcinomas, not only the frequency of occurrence is different in men and women, but also whether the malignancies concerned are mono- or polyclonal. The clonality of cancer cells, therefore, appears to be associated with gender.

The researchers suspected so far that possible differences in the occurrence of individual tumor entities and the response to therapy in men and women could at least partially be explained by gender-specific differences. However, no such link has been demonstrated so far.

What do we already know?

It has been known for some time that tumor incidences of the individual entities differ. For example, the age-standardized new disease rate for lung cancer in Germany is about 57.3/100,000 for men and about 29.0/100,000 for women. Bowel cancer occurs with 54.0/100,000 for men and 35.7/100,000 for women.

In addition, patients also die differently frequently at their respective tumor entities. For lung cancer, for example, the mortality rate is about twice as high for men as for women, and still a factor of 1.6 for colon cancer.

The results make  gender-associated differences clear

Nonetheless, six oncogenic DNA regions were found in the genetic assessments of the study, which differed in their mutation frequency between men and women. At the top of the list were known marker genes such as CTNNB1, ALB, and PTCH1.

However, the largest genomic gender differences were found in the so-called TERT promoter. In the male tissue samples, mutations were found in 64% of the cases, in the women only 11%. Men also tended to have a higher mutation rate per malignancy than women.

Is this significant in medical practice?

These data show once again how important it is to characterize tumors genetically, especially if this can have direct effects on the therapy decisions. Only recently, a further meta-analysis showed that men with certain tumor diseases responded significantly better to immunotherapy with checkpoint inhibitors than women.

However, such data are not only important for treatment planning but also influence the recruitment and characterization of patients seen in oncological studies. All in all, the respective sex should be in the future included in the therapy planning of various malignancies, the study authors concluded.

Sources:
1. Li CH et al., Sex Differences in Oncogenic Mutational Processes. BioRxiv 2019; DOI: http://dx.doi.org/10.1101/528968
2. Conforti F et al., Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis. Lancet Oncol 2018; http://dx.doi.org/10.1016/S 1470-2045(18)30261-4

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