Characterization of Molecular Differences in Cancer Between Male and Female Patients
It is well known that men and women differ in terms of cancer susceptibility, survival, and mortality, but exactly why this occurs at a molecular level has been poorly understood. A study at The University of Texas MD Anderson Cancer Center reviewed 13 cancer types and provided a molecular understanding of sex effects in diverse cancers. The research revealed two cancer-type groups associated with cancer incidence and mortality, suggesting a “pressing need” to develop sex-specific therapeutic strategies for some cancers. The research findings were published by Yuan et al in Cancer Cell.
Using data from The Cancer Genome Atlas, a team led by Han Liang, PhD, Associate Professor of Bioinformatics and Computational Biology, found that more than half of the genes studied showed sex-biased signatures in certain cancer types.
“Our study helps elucidate the molecular basis for sex disparities in cancer and lays a critical foundation for the future development of precision cancer medicine that is sex-specific,” said Dr. Liang. “This is a crucial finding as currently, male and female patients with many cancer types often are treated in a similar way without explicitly considering their gender.”
Study Details
Dr. Liang’s group performed a comprehensive analysis of molecular differences between male and female patients, revealing two sex-effect groups associated with distinct incidence and mortality profiles and accounting for 53% of clinically actionable genes. Those genes are informative for clinical decisions and are either therapeutic targets or biomarkers that can help predict patient survival or tumor response.
In the study, Dr. Liang found one group contained a small number of sex-affected genes (“weak” group), while the other showed a much greater number of sex-biased molecular signatures (“strong” group). Dr. Liang said the current equal treatment of both genders may be appropriate for those in the weak group, but observations in the strong group are clinically significant.
“Special consideration should be given to those in the strong sex-effect group in terms of both drug development and practice,” said Dr. Liang. “For a therapeutic target with a strong sex-biased signature, sex-specific clinical trials may be more likely to succeed. This new information is vital, as the fundamental issue of sex differences for cancer prevention and therapy has not been investigated systematically.”
Dr. Liang’s team analyzed data in patient cohorts of 30 or greater samples for each sex for various cancers of the bladder, colon, kidney, brain, rectum, thyroid, liver, and lung, as well as acute myeloid leukemia. They looked for specific molecular data including somatic mutations, copy alterations, protein and gene expression, and DNA methylation. The study included controls for other factors such as race, age, disease stage, smoking status, and tumor purity.
“Interestingly, our analysis also suggested that sex bias might be amplified during the tumor formation process,” said Dr. Liang. “However this observation should be interpreted with caution at this early stage, as further efforts are needed to determine the relative contributions of other factors, including tumorigenesis, sex chromosomes, and hormones.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
