Glioma is the most common type of primary malignant brain tumor in the United States; glioblastoma being the most common type of glioma in adults. While sex differences in the incidence and survival rates of glioma were known, researchers had not investigated whether genetic differences based on sex could cast light on potential differences in the risk profile of glioma between men and women.
Now, researchers have discovered that men and women have different genetic risk factors for developing glioma. The research was recently published in Scientific Reports. The study involved the work of more than 35 investigators representing more than 30 universities, institutes and government agencies worldwide.
"Sex-stratified analyses in studies such as this can reveal novel insights into the known sex differences in glioma and provide previously unknown genetic risk associations," said one of the authors of the study. "This finding could provide an avenue to gaining a better understanding of sex differences in brain tumor incidence, and may also suggest varying mechanisms and pathways of the disease."
The consortium looked at the genetic differences among all glioma, glioblastoma only and non-glioblastoma patients based on their sex. The researchers found three regions in the genome where significant genetic differences between men and women existed, and these differences also varied by sex and type of tumor (glioblastoma vs. non-glioblastoma).
A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
"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," the author said.
Though early in the process of understanding the genetic sources of sex based differences in malignant brain tumors, the recent analysis could help define a path to a genetic test that helps doctors assess patient risk for brain cancer.
"We were surprised to find a large region in the genome associated with glioma and specifically glioblastoma in females only," the author said. "This region had not previously been associated with gliomas, although other similar genome-wide associated studies have identified associations at this region for a variety of traits, including several autoimmune diseases, as well as increased age at menarche." As the study discussion notes, if increased lifetime estrogen exposure decreases glioma risk, as some have hypothesized, it is possible that variants which increase age at menarche (potentially decreasing total estrogen exposure) may increase glioma risk in females.
Men and women have different genetic risk factors for developing brain cancer
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