According to studies, the incidence of, and survival rates for, gliomas differ between males and females. However, the influence of sex-specific genetic differences on the risk profile of glioma was poorly understood by scientists until a recent study revealed that different genetic risk factors dictate the development of glioma in males and females.
In their article, published in the journal Scientific Reports, an international team led by researchers from Case Western Reserve University School of Medicine (CaseMed) in Ohio identified regions in the human genome where genetic variations occurred based on gender and types of tumor. The team believes that understanding these variations could one day lead to a genetic test that can help clinicians assess a patient's risk of brain cancer.
Gliomas are generally classified into either glioblastoma, which constitutes 61.9 percent of adult glioma cases in America, and low-grade glioma, which occurs only in 24.2 percent of adult glioma cases.
Research shows that glioblastoma has a low 5-year survival rate of only five percent. This means that people with this disease are, on average, only five percent as likely as healthy people to live for at least five years after receiving their diagnoses. (Related: Researchers discover a compound in evodia that can potentially be used for glioblastoma cancer treatments.)
Age and race or ethnicity are believed to influence the incidence of glioma substantially. In the U.S., the lifetime risk of developing gliomas is more than twice as high among non-Hispanic whites than blacks. Statistics also show that it is 25 percent higher in non-Hispanic whites than Hispanic whites.
Globally, the highest incidence rates for glioma can be found in the U.S., Canada, Australia and Northern Europe. Studies also reveal that survival rates after a glioma diagnosis vary by race or ethnicity.
While many environmental factors are implicated in the development of gliomas, so far, the only validated risk factors for these tumors are ionizing radiation, which increases a person's risk, and a history of allergies and other atopic diseases, which decreases the risk.
According to the latest studies, the incidence of glioma is approximately 50 percent higher in males, potentially owing to sex hormones in women, which are believed to play a protective role against the disease. However, existing literature on this report inconsistent results.
For their study, the researchers looked at the genetic differences between patients with glioma, glioblastoma only and non-glioblastoma based on their sex. They focused specifically on autosomal single nucleotide polymorphisms (SNPs) and sex chromosome variants. While the former refers to mutations present in genes form non-sex chromosomes, the latter refers to variations specific to genes in the sex chromosomes only.
The researchers found three regions in the genome where genetic differences between men and women existed. Two of them were previously identified risk loci while the other was a newly identified autosomal locus. The genetic differences, they noted, varied based on gender and type of tumor (i.e., glioblastoma vs. non-glioblastoma).
“There’s one where it’s clearly associated with an increased risk in males, one where it’s clearly associated with an increased risk in females, and one where it’s showing in both males and females, but it seems to have a stronger association in females,” said Jill Barnholtz-Sloan, a professor at CaseMed and senior author of the study.
“These significant differences in effect size,” noted Barnholtz-Sloan and her team in their report, “may be a result of differing biological function of these variants by sex due to biological sex differences, or interaction between these variants and unidentified risk factors that vary in prevalence or effect by sex.”