Genetics Help Explain Why Cancer Affects Men and Women Differently

An analysis of data from 3,200 male and female patients with 13 cancer types enrolled in the Cancer Genome Atlas database reveals that molecular differences may cause men and women to experience cancer differently.

“An individual’s sex has been long recognized as a key factor affecting cancer incidence, prognosis, and treatment responses,” study authors explained. “However, the molecular basis for sex disparities in cancer remains poorly understood.”

In the study, published in Cancer Cell, researchers compared mutation rates and levels of certain proteins present in cancer tumor cells in male and female patients, finding significant differences in the properties of cancer-related genes between men and women.

For eight cancer types, these differences in molecular characteristics were strongly associated with distinct incidence and mortality profiles in men and women:

  • thyroid carcinoma
  • head and neck squamous cell carcinoma
  • lung squamous cell carcinoma
  • lung adenocarcinoma
  • liver hepatocellular carcinoma
  • bladder urothelial carcinoma
  • kidney renal papillary cell carcinoma
  • kidney renal clear cell carcinoma

For five other cancer types (glioma, glioblastoma, colon cancer, rectal cancer, and acute myeloid leukemia), the relationship was weaker.

Of the 114 actionable genes (those considered potential targets for precision medicine), 53 percent (n=60) showed sex-biased signatures. For example, the STK11 gene was deleted in 23 percent of cases of lung cancer in men compared with 11 percent in women. In kidney cancer patients, researchers found a gender effect in some genes that are targeted by immunotherapy drugs suggesting that, in some cases, patients’ sex may provide insight into treatment responses.

The authors noted that the findings could eventually affect drug development and clinical trials, as well as guide health-care providers in preventing and treating cancers by taking a patient’s sex into account.


Yuan Y, Liu L, Chen H, et al. Comprehensive characterization of molecular differences in cancer between male and female patients. Cancer Cell. 2016;29:711-22.