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Research Highlight | December 14, 2020

Why does sex affect cancer? New study reveals oncogenomic differences between males and females

Researchers know that cancer affects males and females differently. For example, for most tumour types, males are at a higher risk of being diagnosed with cancer and dying from the disease, even after adjusting for known risk factors. But despite this knowledge, the reasons behind these disparities have remained relatively unknown.

A new study led by former Terry Fox New Investigator Dr. Paul Boutros reveals key differences in specific genes and in genome-wide phenomena that may explain why cancer progresses differently in males and females.

“Our study demonstrates that there are genomic differences between sexes that explain why many cancers evolve differently depending on whether they arise in males or females,” said Dr. Boutros, director of cancer data science, University of California, Los Angeles. “These evolutionary differences help explain why some cancers escape therapy and become lethal.”

To make these findings, the team analyzed 1,983 samples of 28 cancer subtypes gathered through the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. Cancers affecting sex organs were excluded from the study. After analyzing coding and non-coding regions of the DNA, the team discovered oncogenomic differences between tumours of males and females in three key areas: the number of mutations affecting them, the types of mutations they harboured, and their overall evolution.

These sex-biases suggest differences in the origins and trajectories of tumours between males and females, which according to the paper published in Nature Communications (August 2020), are influenced by both endogenous and environmental factors.

For Dr. Boutros, uncovering these differences is key to improving how cancer patients are managed.

“By understanding why cancers differ, we can better learn to personalize treatment for each individual patient, improving their outcomes,” said Dr. Boutros.

This study is part of a series of papers by Dr. Boutros and his PhD student Dr. Constance Li, that have explored how key features of the patient influence cancer evolution.  Beyond sex, the team has demonstrated that patient age and ancestry also influence the evolution of cancers.

“These findings suggest that, moving forward, all studies of cancer need to consider at least these three factors,” said Dr. Boutros.

Study

Sex differences in oncogenic mutational processes

Authors

Constance H. Li, Stephenie D. Prokopec, Ren X. Sun, Fouad Yousif, Nathaniel Schmitz, PCAWG Tumour Subtypes and Clinical Translation, Paul C. Boutros & PCAWG Consortium

Funding

This study was partially funded by a Terry Fox New Investigator Award in Systems Biology of Tumour Hypoxia to Dr. Paul Boutros