The team analyzed molecular-level differences between approximately 3,200 males and females with cancer using an analytic approach based on the propensity score, a statistical tool that allowed researchers to adjust for confounding factors such as age, race, disease stage, and tumor purity. Investigators focused on 13 major cancer types, including head and neck squamous cell carcinoma (HNSCC) and thyroid carcinoma, for at least five out of six molecular data types.
Examining the global patterns of sex-biased genes across different molecular types, the investigators found a clear separation among the cancer types under survey, with the cancer types in the strong sex-effect group showing a higher cancer incidence sex-bias index and a higher mortality sex-bias index. Their findings were reinforced by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology, which suggest a patient’s sex as a prognostic factor in five of the eight strong sex-effect cancers named in the study.
Researchers focused on highly mutated genes in each cancer type and identified specific biases toward males or females. Study authors acknowledge, however, that their analysis based on the mRNA expression data of related TCGA normal samples “detected much fewer sex-biased genes, suggesting the sex bias might be amplified during the tumorigenesis process.” They also go on to point out that the so-called normal tissues analyzed consisted of distinct cell types from the corresponding tumor samples, thus potentially confounding the observable tumor-normal differences. In addition, the normal tissues’ sample size was significantly smaller than that of the tumor samples, possibly limiting “detection power.” The authors conclude that further efforts are required to shed more light on the “relative contributions of various factors (e.g., sex chromosomes, hormones, and tumorigenesis) to the observed sex-biased gene expression signatures in cancer samples.”
Thyroid, and Head and Neck Cancers
Thyroid cancer, one of the study’s identified strong sex-effect cancers, is already known to have a gender bias. A review by Yao and colleagues discusses results of the epidemiological, clinical, and experimental research on the role of sex hormones, their receptors, and other molecular factors in the higher incidence of thyroid cancer in women (Expert Rev Endocrinol Metab. 2011;6(2):215-243).
“We see that papillary thyroid cancer is four times more common in women than in men,” said Erich M. Sturgis, MD, MPH, professor in the departments of head and neck surgery and epidemiology at MDACC. “You would assume the underlying reasons for that might suggest that the mutation patterns in men and women are different because the background in which it arises is different and that attributing factors, such as hormone level, are an important component of thyroid cancer.”