Sex Biases in Cancer and Autoimmune Disease Incidence Are Strongly Positively Correlated with Mitochondrial Gene Expression across Human Tissues

SIMPLE SUMMARY: Our study investigates the well-known observation/quandary that cancer occurs more frequently in men while autoimmune diseases (AIDs) occur more frequently in women. This has motivated us to explore whether these sex biases may have a common basis. To study that, we assembled and analyzed a large collection of cancer and AID incidence datasets, including matched data from 29 countries. We first, quite strikingly, find that the sex biases observed in the incidence of AIDs and cancers that occur in the same tissue are positively correlated across human tissues. To our knowledge, this is the first time this across-tissue relationship has been quantitatively demonstrated. Second, we find by analyzing healthy human tissue gene expression data that the sex bias in the expression of mitochondrial-encoded genes stands out as the common key factor whose levels across human tissues are most strongly and positively associated with both cancer and AID incidence rate sex biases, pointing to the key potential role of these genes in determining sex bias in both disorders. These findings may further prompt researchers to explore how pertaining findings in cancer studies could cross fertilize AID studies and vice versa, potentially enhancing our ability to prevent and treat these diseases. ABSTRACT: Cancer occurs more frequently in men while autoimmune diseases (AIDs) occur more frequently in women. To explore whether these sex biases have a common basis, we collected 167 AID incidence studies from many countries for tissues that have both a cancer type and an AID that arise from that tissue. Analyzing a total of 182 country-specific, tissue-matched cancer-AID incidence rate sex bias data pairs, we find that, indeed, the sex biases observed in the incidence of AIDs and cancers that occur in the same tissue are positively correlated across human tissues. The common key factor whose levels across human tissues are most strongly associated with these incidence rate sex biases is the sex bias in the expression of the 37 genes encoded in the mitochondrial genome.