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

David R Crawford; Sanju Sinha; Nishanth Ulhas Nair; Bríd M Ryan; Jill S Barnholtz-Sloan; Stephen M Mount; Ayelet Erez; Kenneth Aldape; Philip E Castle; Padma S Rajagopal; Chi-Ping Day; Alejandro A Schäffer; Eytan Ruppin

doi:10.3390/cancers14235885

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

Cancers (Basel). 2022 Nov 29;14(23):5885. doi: 10.3390/cancers14235885.

Authors

David R Crawford^{1

2

3}, Sanju Sinha¹, Nishanth Ulhas Nair¹, Bríd M Ryan⁴, Jill S Barnholtz-Sloan^{5

6}, Stephen M Mount², Ayelet Erez⁷, Kenneth Aldape⁸, Philip E Castle^{6

9}, Padma S Rajagopal^{1

10}, Chi-Ping Day¹¹, Alejandro A Schäffer¹, Eytan Ruppin¹

Affiliations

¹ Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
² Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
³ Graduate Program in Computational Biology, Bioinformatics, and Genomics, University of Maryland, College Park, MD 20742, USA.
⁴ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁵ Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁶ Trans-Divisional Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁷ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610000, Israel.
⁸ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁹ Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹⁰ Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹¹ Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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.

Keywords: autoimmune disease incidence; autoimmunity; cancer incidence; immunity; inflammation; mitochondria; sex bias.

Grants and funding

This research received no external funding.