In addition to the known sex-specific cancer types, such as ovarian and prostate cancers, there are significant disparities between the sexes in in non–sex-specific cancers, such as rate of incidence and susceptibility, tumor aggressiveness, prognosis, and treatment response. A recent study published in Cancer Cell explored the molecular basis for these differences (Cancer Cell. 2016;29:711-722).
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December 2016Although the medical research community has long understood that gender can influence the development and behavior of tumors in patients, this study provides a systematic, molecular-level analysis of gender differences as they present themselves in diverse cancers. It underscores the potential for developing sex-specific therapeutic strategies to prevent and treat certain cancer types, including those of the thyroid and head and neck.
Among the cancer types analyzed, the study’s findings identified two sex-effect groups of cancers associated with distinct incidence and mortality profiles: a strong sex-effect group that showed extensive sex-biased molecular signatures and a weak sex-effect group that contained a small number of sex-affected genes. More than 50% of clinically actionable genes showed sex-biased molecular signatures in certain cancer types.
Strong sex-effect cancers identified in the study included those of the thyroid and head and neck, as well as bladder, liver, and two types each of lung and kidney cancers. Cancers in the weak sex-effect group included specific brain tumors (glioma and glioblastoma), colon and rectum cancers, and acute myeloid leukemia.
Previous studies that have reported sex-related molecular patterns have been limited to individual genes, single molecular data types, and single cancer lineages. Another recent study identified H3K27me3 demethylase UTX as a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia, a cancer that has shown a skewed distribution toward males (Blood. 2015;125:13-21).
With this study, researchers sought to advance understanding of gender differences with a systematic, multidimensional analysis of sex-affected genes. “So, you take two patients with oropharyngeal cancer although they didn’t look specifically at patients with oropharyngeal cancer—they hypothesize that for this and other cancers the outcomes may be very different for a male versus a female,” said Randal S. Weber, MD, FACS, professor in and chair of the department of head and neck surgery at the University of Texas MD Anderson Cancer Center (MDACC) in Houston. “What they found is that their tumors have different genetic signatures or profiles, so it may explain why a male’s prognosis might be different from a female’s.”
Molecular Signatures
For the study, researchers used molecular data available through The Cancer Genome Atlas (TCGA) Project to perform a comprehensive, rigorous, pan-cancer analysis. The goal: to address whether or not there are molecular-level differences between the male and female cancer patients who have otherwise similar clinical and tumor characteristics and, if so, to identify them.